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Title:

Octanoic acid a major component of widely consumed medium-chain triglyceride ketogenic diet is detrimental to bone

Authors:

Jain, Shreshta; Rai, Reena; Singh, Divya; Vohora, Divya

Abstract:

Octanoic acid is a medium-chained saturated fatty acid found abundantly in the ketogenic dietary supplements containing medium chained triglycerides (MCT) along with decanoic acid. The MCT ketogenic diet is commonly consumed for weight loss but has also showcased neuroprotective potential against neurodegenerative disorders. However, recent clinical findings have reported a critical disadvantage with the long-term consumption of ketogenic diet i.e. bone loss. The following study was employed to investigate whether the two major components of MCT diet also possess bone loss potential as observed with classical ketogenic diet. Swiss albino mice aged between 10 and 12 weeks, were divided into 3 treatment groups that were administered with oral suspensions of octanoic acid, decanoic acid and a combination of both for 4 weeks. Bone specific markers, microarchitectural parameters, using micro computed tomography, and biomechanical strength were analyzed. Remarkably deleterious alterations in the trabecular bone microarchitecture, and on bone markers were observed in the octanoic acid treated groups. Our results suggest significant negative effects on bone health by octanoic acid. These findings require further investigation and validation in order to provide significant clinically relevant data to possibly modify dietary composition of the MCT ketogenic diet.

Published:

March 26, 2021

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Title:

Time-Restricted Eating to Improve Cardiovascular Health

Authors:

Gabel, Kelsey; Cienfuegos, Sofia; Kalam, Faiza; Ezpeleta, Mark; Varady, Krista A.

Abstract:

PURPOSE OF REVIEW: Time-restricted eating (TRE) is a form of intermittent fasting that involves confining the eating window to 4-10 h and fasting for the remaining hours of the day. The purpose of this review is to summarize the current literature pertaining to the effects of TRE on body weight and cardiovascular disease risk factors. RECENT FINDINGS: Human trial findings show that TRE reduces body weight by 1-4% after 1-16 weeks in individuals with obesity, relative to controls with no meal timing restrictions. This weight loss results from unintentional reductions in energy intake (~350-500 kcal/day) that occurs when participants confine their eating windows to 4-10 h/day. TRE is also effective in lowering fat mass, blood pressure, triglyceride levels, and markers of oxidative stress, versus controls. This fasting regimen is safe and produces few adverse events. These findings suggest that TRE is a safe diet therapy that produces mild reductions in body weight and also lowers several key indicators of cardiovascular disease in participants with obesity.

Published:

March 26, 2021

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Title:

Acutely increased β-hydroxybutyrate plays a role in the prefrontal cortex to escape stressful conditions during the acute stress response

Authors:

Son, Hyeonwi; Baek, Ji Hyeong; Kang, Jae Soon; Jung, Soonwoong; Chung, Hye Jin; Kim, Hyun Joon

Abstract:

Ketone bodies can be increased in the blood under certain physiological conditions, but their role under such conditions remains to be clarified. In the present study, we found the increment and usage of β-hydroxybutyrate (BHB) in the prefrontal cortex (PFC) during acute stress. BHB levels increased in the blood and PFC after 30-min acute immobilization stress, and BHB dehydrogenase 1 increased in the PFC simultaneously, but not in the hippocampus. Moreover, increased levels of acetyl-CoA, pyruvate carboxylase, and glutamate dehydrogenase 1 were found in the PFC, implicating the metabolism of increased BHB in the brain. Thus, we checked the levels of glutamate, glutamine, and GABA and found increased levels of glutamate and glutamine in the stressed group compared with that in the control group in the PFC. Exogenous administration of BHB enhanced struggling behaviors under stressful conditions. Our results suggest that the metabolism of BHB from peripheral blood in the PFC may contribute to acute stress responses to escape stressful conditions.

Published:

March 25, 2021

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Title:

Dietary carbohydrate and energy expenditure: Exploring biological mechanisms of body-weight control

Authors:

Abstract:

A meta-analysis of 29 controlled-feeding studies sheds new light on the relation between macronutrient composition and total energy expenditure, according Read More

Published:

March 25, 2021

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Title:

Human evolution: Thumbs up for efficiency

Authors:

Kivell, Tracy L.

Abstract:

Published:

March 22, 2021

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Title:

A ketogenic diet impacts markers of mitochondrial mass in a tissue specific manner in aged mice

Authors:

Zhou, Zeyu; Hagopian, Kevork; José L&#xF3, A.; pez-Domí nguez; Kim, Kyoungmi; Jasoliya, Mittal; Roberts, Megan N.; Cortopassi, Gino A.; Showalter, Megan R.; Roberts, Bryan S.; José Gonz&#xE1, A.; lez-Reyes; Baar, Keith; Rutkowsky, Jennifer; Ramsey, Jon J.

Abstract:

Aging | doi:10.18632/aging.202834. Zeyu Zhou, Kevork Hagopian, José A. López-Domínguez, Kyoungmi Kim, Mittal Jasoliya, Megan N. Roberts, Gino A. Cortopassi, Megan R. Showalter, Bryan S. Roberts, José A. González-Reyes, Keith Baar, Jennifer Rutkowsky, Jon J. Ramsey

Published:

March 18, 2021

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Title:

Overconsumption of Omega-6 Polyunsaturated Fatty Acids (PUFAs) versus Deficiency of Omega-3 PUFAs in Modern-Day Diets: The Disturbing Factor for Their “Balanced Antagonistic Metabolic Functions” in the Human Body

Authors:

Mariamenatu, Abeba Haile; Abdu, Emebet Mohammed

Abstract:

Polyunsaturated fatty acids (PUFAs) contain ≥2 double-bond desaturations within the acyl chain. Omega-3 (n-3) and Omega-6 (n-6) PUFAs are the two known important families in human health and nutrition. In both Omega families, many forms of PUFAs exist: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) from the n-3 family and linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA) from the n-6 family are the important PUFAs for human health. Omega-3 and Omega-6 PUFAs are competitively metabolized by the same set of desaturation, elongation, and oxygenase enzymes. The lipid mediators produced from their oxidative metabolism perform opposing (antagonistic) functions in the human body. Except for DGLA, n-6 PUFA-derived lipid mediators enhance inflammation, platelet aggregation, and vasoconstriction, while those of n-3 inhibit inflammation and platelet aggregation and enhance vasodilation. Overconsumption of n-6 PUFAs with low intake of n-3 PUFAs is highly associated with the pathogenesis of many modern diet-related chronic diseases. The volume of n-6 PUFAs is largely exceeding the volume of n-3PUFAs. The current n-6/n-3 ratio is 20-50/1. Due to higher ratios of n-6/n-3 in modern diets, larger quantities of LA- and AA-derived lipid mediators are produced, becoming the main causes of the formation of thrombus and atheroma, the allergic and inflammatory disorders, and the proliferation of cells, as well as the hyperactive endocannabinoid system. Therefore, in order to reduce all of these risks which are due to overconsumption of n-6 PUFAs, individuals are required to take both PUFAs in the highly recommended n-6/n-3 ratio which is 4-5/1.

Published:

March 17, 2021

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Title:

Spontaneous Coronary-Artery Dissection

Authors:

Abstract:

Correspondence from The New England Journal of Medicine — Spontaneous Coronary-Artery Dissection

Published:

March 17, 2021

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Title:

Cannabinoid Receptors Overexpression in a Rat Model of Irritable Bowel Syndrome (IBS) after Treatment with a Ketogenic Diet

Authors:

Gigante, Isabella; Tutino, Valeria; Russo, Francesco; De Nunzio, Valentina; Coletta, Sergio; Armentano, Raffaele; Crovace, Alberto; Caruso, Maria Gabriella; Orlando, Antonella; Notarnicola, Maria

Abstract:

The administration of a ketogenic diet (KD) has been considered therapeutic in subjects with irritable bowel syndrome (IBS). This study aimed to investigate the molecular mechanisms by which a low-carbohydrate diet, such as KD, can improve gastrointestinal symptoms and functions in an animal model of IBS by evaluating possible changes in intestinal tissue expression of endocannabinoid receptors. In rats fed a KD, we detected a significant restoration of cell damage to the intestinal crypt base, a histological feature of IBS condition, and upregulation of CB1 and CB2 receptors. The diet also affected glucose metabolism and intestinal membrane permeability, with an overexpression of the glucose transporter GLUT1 and tight junction proteins in treated rats. The present data suggest that CB receptors represent one of the molecular pathways through which the KD works and support possible cannabinoid-mediated protection at the intestinal level in the IBS rats after dietary treatment.

Published:

March 12, 2021

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Title:

Complex evolutionary history of two ecologically significant grass genera, Themeda and Heteropogon (Poaceae: Panicoideae: Andropogoneae)

Authors:

Arthan, Watchara; Dunning, Luke T; Besnard, Guillaume; Manzi, Sophie; Kellogg, Elizabeth A; Hackel, Jan; Lehmann, Caroline E R; Mitchley, Jonathan; Vorontsova, Maria S

Abstract:

Themeda and Heteropogon are closely related grass genera frequently dominant in tropical C4 grasslands. Relationships between them are poorly resolved, impeding ecological study, especially of T. triandra with a broad distribution from Africa to East Asia, and H. contortus with a pantropical distribution. Our analyses of plastome and nuclear genomes with comprehensive sampling of Themeda and Heteropogon demonstrate that neither genus is monophyletic as currently circumscribed. Plastome and nuclear data place H. melanocarpus and H. ritchiei in Themeda. Nested in T. triandra are T. quadrivalvis and T. unica, demonstrating that this widespread species is more morphologically diverse than previously recognized. Heteropogon fischerianus is nested in H. contortus. The picture is more complex for H. triticeus that is sister to H. contortus in the nuclear analysis and to Cymbopogon in the plastome analysis. This incongruence between nuclear and plastid phylogenetic trees suggests hybridization between Cymbopogon-related genome donors and H. contortus. Plastome dating estimates the Themeda–Heteropogon crown age at c. 7.6 Myr, consistent with the Miocene C4 grassland expansion. Themeda triandra and H. contortus diversified 1–2 Mya in the Pleistocene. These results establish a foundation for studying the history of these ecologically significant widespread grasses and the ecosystems they form.

Published:

March 9, 2021

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Title:

Perspective: The Saturated Fat–Unsaturated Oil Dilemma: Relations of Dietary Fatty Acids and Serum Cholesterol, Atherosclerosis, Inflammation, Cancer, and All-Cause Mortality

Authors:

Lawrence, Glen D

Abstract:

PUFAs are known to regulate cholesterol synthesis and cellular uptake by multiple mechanisms that do not involve SFAs. Polymorphisms in any of the numerous proteins involved in cholesterol homeostasis, as a result of genetic variation, could lead to higher or lower serum cholesterol. PUFAs are susceptible to lipid peroxidation, which can lead to oxidative stress, inflammation, atherosclerosis, cancer, and disorders associated with inflammation, such as insulin resistance, arthritis, and numerous inflammatory syndromes. Eicosanoids from arachidonic acid are among the most powerful mediators that initiate an immune response, and a wide range of PUFA metabolites regulate numerous physiological processes. There is a misconception that dietary SFAs can cause inflammation, although endogenous palmitic acid is converted to ceramides and other cell constituents involved in an inflammatory response after it is initiated by lipid mediators derived from PUFAs. This article will discuss the many misconceptions regarding how dietary lipids regulate serum cholesterol, the fact that all-cause death rate is higher in humans with low compared with normal or moderately elevated serum total cholesterol, the numerous adverse effects of increasing dietary PUFAs or carbohydrate relative to SFAs, as well as metabolic conversion of PUFAs to SFAs and MUFAs as a protective mechanism. Consequently, dietary saturated fats seem to be less harmful than the proposed alternatives.

Published:

March 9, 2021

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Title:

The evolution of the human trophic level during the Pleistocene

Authors:

Ben‐Dor, Miki; Sirtoli, Raphael; Barkai, Ran

Abstract:

The human trophic level (HTL) during the Pleistocene and its degree of variability serve, explicitly or tacitly, as the basis of many explanations for human evolution, behavior, and culture. Previous attempts to reconstruct the HTL have relied heavily on an analogy with recent hunter-gatherer groups' diets. In addition to technological differences, recent findings of substantial ecological differences between the Pleistocene and the Anthropocene cast doubt regarding that analogy's validity. Surprisingly little systematic evolution-guided evidence served to reconstruct HTL. Here, we reconstruct the HTL during the Pleistocene by reviewing evidence for the impact of the HTL on the biological, ecological, and behavioral systems derived from various existing studies. We adapt a paleobiological and paleoecological approach, including evidence from human physiology and genetics, archaeology, paleontology, and zoology, and identified 25 sources of evidence in total. The evidence shows that the trophic level of the Homo lineage that most probably led to modern humans evolved from a low base to a high, carnivorous position during the Pleistocene, beginning with Homo habilis and peaking in Homo erectus. A reversal of that trend appears in the Upper Paleolithic, strengthening in the Mesolithic/Epipaleolithic and Neolithic, and culminating with the advent of agriculture. We conclude that it is possible to reach a credible reconstruction of the HTL without relying on a simple analogy with recent hunter-gatherers' diets. The memory of an adaptation to a trophic level that is embedded in modern humans' biology in the form of genetics, metabolism, and morphology is a fruitful line of investigation of past HTLs, whose potential we have only started to explore.

Published:

March 5, 2021

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Title:

The whiteness of the Mediterranean Diet: A historical, sociopolitical, and dietary analysis using Critical Race Theory

Authors:

Burt, Kate

Abstract:

Ample evidence indicates that adherence to the Mediterranean diet (MedDiet) decreases the risk of cardiovascular disease, stroke, heart failure, cancer mortality, type 2 diabetes, overweight, and obesity. The MedDiet is widely accepted as a gold standard diet, yet its adoption and promotion as the healthiest cultural diet reflects systemic racism and inherently biased research, rather than evidence-based science. This analysis establishes that while the Mediterranean region is multi-cultural and multi-ethnic, the MedDiet is a White diet. It also asserts that a lack of causal research and other methodologic issues in research about the MedDiet has resulted in a hyperfocus on the MedDiet over other cultural diets. Third, this essay compares the MedDiet to the traditional Chinese and African diets to assert that many cultural diets are healthy and may be as healthy as the MedDiet. Ultimately, health professionals promoting the MedDiet as a gold standard marginalize people from non-White cultures by maintaining White culture as normative. In order to better serve and include people of color, dietary recommendations need to become as diverse as the US population. Doing so will also improve cultural competence among professionals, lead to a more equitable profession

Published:

March 4, 2021

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Title:

Hunting of mammals by central chimpanzees (Pan troglodytes troglodytes) in the Loango National Park, Gabon

Authors:

Klein, Harmonie; Bocksberger, Gaëlle; Baas, Pauline; Bunel, Sarah; Théleste, Erwan; Pika, Simone; Deschner, Tobias

Abstract:

The predation and consumption of animals are common behaviours in chimpanzees across tropical Africa. To date, however, relatively little is known concerning the hunting behaviour of central chimpanzees (Pan troglodytes troglodytes). Here, we provide the first direct observations of hunting behaviour by individuals of the newly habituated Rekambo community in the Loango National Park, Gabon. Over a period of 23 months (May 2017 to March 2019), we observed a total of 61 predation attempts on eight mammal species, including four monkey species. The two most frequently hunted species were two monkey species (Cercocebus torquatus, Cercopithecus nictitans), which are not hunted at other long-term field sites. The majority of predation events observed involved parties of an average of eight individuals, mainly adult males, with hunting success being higher with increasing numbers of participants. Hunting occurred all year round, but hunting rates increased in the dry season, the period of high fruit availability in the Loango National Park. These results are in line with the nutrient surplus hypothesis which explains seasonal variation in hunting behaviour in several populations of eastern chimpanzees (Pan troglodytes schweinfurthii: e.g., Mahale, Tanzania; Ngogo, Uganda). Finally, with a hunting frequency of 2.65 hunts per month, the Rekambo community had higher hunting rates than other sites (Bossou, Republic of Guinea; Kahuzi-Biega, Democratic Republic of Congo; Budongo, Uganda) where red colobus monkeys are also absent. We discuss these results and compare them to patterns at other long-term sites.

Published:

March 1, 2021

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Title:

Leisure time physical activity throughout adulthood is associated with lower medicare costs: evidence from the linked NIH-AARP diet and health study cohort

Authors:

Coughlan, Diarmuid; Saint-Maurice, Pedro F.; Carlson, Susan A.; Fulton, Janet; Matthews, Charles E.

Abstract:

Background

There is limited information about the association between long-term leisure time physical activity (LTPA) participation and healthcare costs. The purpose of this study was to investigate the association between LTPA over adulthood with later life healthcare costs in the USA.

Methods

Using Medicare claims data (between 1999 and 2008) linked to the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, we examined associations between nine trajectories of physical activity participation throughout adulthood with Medicare costs.

Results

Compared with adults who were consistently inactive from adolescence into middle age, average annual healthcare costs were significantly lower for maintainers, adults who maintained moderate (–US$1350 (95% CI: –US$2009 to –US$690) or −15.9% (95% CI: −23.6% to −8.1%)) or high physical activity levels (–US$1200 (95% CI: –US$1777 to –US$622) or −14.1% (95% CI: −20.9% to −7.3%)) and increasers, adults who increased physical activity levels in early adulthood (–US$1874 (95% CI: US$2691 to –US$1057) or −22.0% (95% CI: −31.6% to −12.4%)) or in middle age (–US$824 (95% CI: –US$1580 to –US$69 or −9.7% (95% CI −18.6% to −0.8%)). For the four trajectories where physical activity decreased, the only significant difference was for adults who increased physical activity levels during early adulthood with a decline in middle age (–US$861 (95% CI:–US$1678 to –US$45) or −10.1% (95% CI: −19.7% to −0.5%)).

Conclusion

Our analyses suggest the healthcare cost burden in later life could be reduced through promotion efforts supporting physical activity participation throughout adulthood.

Published:

March 1, 2021

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Title:

Prey preferences of modern human hunter-gatherers

Authors:

Bugir, Cassandra K.; Peres, Carlos A.; White, Kevin S.; Montgomery, Robert A.; Griffin, Andrea S.; Rippon, Paul; Clulow, John; Hayward, Matt W.

Abstract:

Understanding traditional hunter-gatherer lifestyles in our modern world is fundamental to our understanding of their viability, as well as the role of humans as predators in structuring ecosystems. Here, we examine the factors that drive prey preferences of modern hunter-gatherer people by reviewing 85 published studies from 161 tropical, temperate and boreal sites across five continents. From these studies, we estimated Jacobs' selectivity index values (D) for 2243 species/spatiotemporal records representing 504 species from 42 vertebrate orders based on a sample size of 799,072 kill records (median = 259). Hunter-gatherers preferentially hunted 11 large-bodied, riskier species, and were capable of capturing species ranging from 0.6 to 535.3 kg, but avoided those smaller than 2.5 kg. Human prey preferences were driven by whether prey were arboreal or terrestrial, the threats the prey afforded hunters, and prey body mass. Variation in the size of prey species pursued by hunter-gatherers across each continent is a reflection of the local size spectrum of available prey, and historical or prehistorical prey depletion during the Holocene. The nature of human subsistence hunting reflects the ability to use a range of weapons and techniques to capture food, and the prey deficient wildlands where people living traditional lifestyles persist.

Published:

March 1, 2021

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Title:

Vegan dietary pattern for the primary and secondary prevention of cardiovascular diseases

Authors:

Rees, Karen; Al-Khudairy, Lena; Takeda, Andrea; Stranges, Saverio

Abstract:

BACKGROUND: Diet plays a major role in the aetiology of cardiovascular disease (CVD) and as a modifiable risk factor is the focus of many prevention strategies. Recently vegan diets have gained popularity and there is a need to synthesise existing clinical trial evidence for their potential in CVD prevention. OBJECTIVES: To determine the effectiveness of following a vegan dietary pattern for the primary and secondary prevention of CVD. SEARCH METHODS: We searched the following electronic databases on 4 February 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Web of Science Core Collection. We also searched ClinicalTrials.gov in January 2021. We applied no language restrictions. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) in healthy adults and adults at high risk of CVD (primary prevention) and those with established CVD (secondary prevention). A vegan dietary pattern excludes meat, fish, eggs, dairy and honey; the intervention could be dietary advice, provision of relevant foods, or both. The comparison group received either no intervention, minimal intervention, or another dietary intervention. Outcomes included clinical events and CVD risk factors. We included only studies with follow-up periods of 12 weeks or more, defined as the intervention period plus post-intervention follow-up. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data and assessed risks of bias. We used GRADE to assess the certainty of the evidence. We conducted three main comparisons: 1. Vegan dietary intervention versus no intervention or minimal intervention for primary prevention; 2. Vegan dietary intervention versus another dietary intervention for primary prevention; 3. Vegan dietary intervention versus another dietary intervention for secondary prevention. MAIN RESULTS: Thirteen RCTs (38 papers, 7 trial registrations) and eight ongoing trials met our inclusion criteria. Most trials contributed to primary prevention: comparisons 1 (four trials, 466 participants randomised) and comparison 2 (eight trials, 409 participants randomised). We included only one secondary prevention trial for comparison 3 (63 participants randomised). None of the trials reported on clinical endpoints. Other primary outcomes included lipid levels and blood pressure. For comparison 1 there was moderate-certainty evidence from four trials with 449 participants that a vegan diet probably led to a small reduction in total cholesterol (mean difference (MD) -0.24 mmol/L, 95% confidence interval (CI) -0.36 to -0.12) and low-density lipoprotein (LDL) cholesterol (MD -0.22 mmol/L, 95% CI -0.32 to -0.11), a very small decrease in high-density lipoprotein (HDL) levels (MD -0.08 mmol/L, 95% CI -0.11 to -0.04) and a very small increase in triglyceride levels (MD 0.11 mmol/L, 95% CI 0.01 to 0.21). The very small changes in HDL and triglyceride levels are in the opposite direction to that expected. There was a lack of evidence for an effect with the vegan dietary intervention on systolic blood pressure (MD 0.94 mmHg, 95% CI -1.18 to 3.06; 3 trials, 374 participants) and diastolic blood pressure (MD -0.27 mmHg, 95% CI -1.67 to 1.12; 3 trials, 372 participants) (low-certainty evidence). For comparison 2 there was a lack of evidence for an effect of the vegan dietary intervention on total cholesterol levels (MD -0.04 mmol/L, 95% CI -0.28 to 0.20; 4 trials, 163 participants; low-certainty evidence). There was probably little or no effect of the vegan dietary intervention on LDL (MD -0.05 mmol/L, 95% CI -0.21 to 0.11; 4 trials, 244 participants) or HDL cholesterol levels (MD -0.01 mmol/L, 95% CI -0.08 to 0.05; 5 trials, 256 participants) or triglycerides (MD 0.21 mmol/L, 95% CI -0.07 to 0.49; 5 trials, 256 participants) compared to other dietary interventions (moderate-certainty evidence). We are very uncertain about any effect of the vegan dietary intervention on systolic blood pressure (MD 0.02 mmHg, 95% CI -3.59 to 3.62)  or diastolic blood pressure (MD 0.63 mmHg, 95% CI -1.54 to 2.80; 5 trials, 247 participants (very low-certainty evidence)). Only one trial (63 participants) contributed to comparison 3, where there was a lack of evidence for an effect of the vegan dietary intervention on lipid levels or blood pressure compared to other dietary interventions (low- or very low-certainty evidence). Four trials reported on adverse events, which were absent or minor. AUTHORS' CONCLUSIONS: Studies were generally small with few participants contributing to each comparison group. None of the included studies report on CVD clinical events. There is currently insufficient information to draw conclusions about the effects of vegan dietary interventions on CVD risk factors. The eight ongoing studies identified will add to the evidence base, with all eight reporting on primary prevention. There is a paucity of evidence for secondary prevention.

Published:

February 25, 2021

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Title:

Betahydroxybutyrate Consumption in Autopsy Brain Tissue from Alzheimer's Disease Subjects

Authors:

Swerdlow, Russell H.; de Leon, Mony J.; Marcus, David L.

Abstract:

Background: Alzheimer's disease (AD) features perturbed brain glucose utilization, which could contribute to brain bioenergetic failure. This led some to consider using ketone bodies to enhance AD brain bioenergetics and treat AD. Objective: We evaluated the rate at which brain homogenates from persons with Alzheimer's disease (AD) metabolize D-β-hydroxybutyrate (BHB). Methods: We homogenized pieces of temporal cortex from frozen autopsy brains obtained from recently deceased AD subjects (n = 4), and age-matched subjects that did not have clinical AD (n = 3). Measuring the rate of CO2 production that followed the introduction of radiolabeled BHB to the homogenates yielded a BHB utilization rate. Results: Compared to the control homogenates, the BHB-supported CO2 production rate was 66%lower in the AD homogenates (p 

Published:

February 24, 2021

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Title:

Betahydroxybutyrate Consumption in Autopsy Brain Tissue from Alzheimer's Disease Subjects

Authors:

Swerdlow, Russell H.; de Leon, Mony J.; Marcus, David L.

Abstract:

Background: Alzheimer's disease (AD) features perturbed brain glucose utilization, which could contribute to brain bioenergetic failure. This led some to consider using ketone bodies to enhance AD brain bioenergetics and treat AD. Objective: We evaluated the rate at which brain homogenates from persons with Alzheimer's disease (AD) metabolize D-β-hydroxybutyrate (BHB). Methods: We homogenized pieces of temporal cortex from frozen autopsy brains obtained from recently deceased AD subjects (n = 4), and age-matched subjects that did not have clinical AD (n = 3). Measuring the rate of CO2 production that followed the introduction of radiolabeled BHB to the homogenates yielded a BHB utilization rate. Results: Compared to the control homogenates, the BHB-supported CO2 production rate was 66%lower in the AD homogenates (p 

Published:

February 24, 2021

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Title:

Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality

Authors:

Jenkins, David J. A.; Dehghan, Mahshid; Mente, Andrew; Bangdiwala, Shrikant I.; Rangarajan, Sumathy; Srichaikul, Kristie; Mohan, Viswanathan; Avezum, Alvaro; Díaz, Rafael; Rosengren, Annika; Lanas, Fernando; Lopez-Jaramillo, Patricio; Li, Wei; Oguz, Aytekin; Khatib, Rasha; Poirier, Paul; Mohammadifard, Noushin; Pepe, Andrea; Alhabib, Khalid F.; Chifamba, Jephat; Yusufali, Afzal Hussein; Iqbal, Romaina; Yeates, Karen; Yusoff, Khalid; Ismail, Noorhassim; Teo, Koon; Swaminathan, Sumathi; Liu, Xiaoyun; Zatońska, Katarzyna; Yusuf, Rita; Yusuf, Salim

Abstract:

Original Article from The New England Journal of Medicine — Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality

Published:

February 24, 2021

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Title:

Intestinal barrier dysfunction in irritable bowel syndrome: a systematic review

Authors:

Hanning, Nikita; Edwinson, Adam L.; Ceuleers, Hannah; Peters, Stephanie A.; De Man, Joris G.; Hassett, Leslie C.; De Winter, Benedicte Y.; Grover, Madhusudan

Abstract:

Background and Aim: Irritable bowel syndrome (IBS) is a complex and heterogeneous disorder. Sensory, motor and barrier dysfunctions are the key physiological endophenotypes of IBS. Our aim is to review studies evaluating barrier dysfunction in adults and children with IBS, as well as to link those changes with IBS symptomatology and quality of life. Methods: A comprehensive and systematic review of multiple databases was performed up to March 2020 to identify studies comparing intestinal permeability in IBS patients with healthy controls. Both in vivo and in vitro studies were considered. Results: We identified 66 studies, of which 27 used intestinal probes to quantify barrier function. The prevalence of barrier dysfunction differed between PI-IBS (17–50%), IBS-D (37–62%) and IBS-C (4–25%). At a group level, permeability was increased compared with healthy controls in IBS-D (9/13 studies) and PI-IBS (4/4 studies), but only a minority of IBS-C (2/7 studies) and not in the only IBS-M study. All four studies in children with IBS demonstrated loss of barrier function. A heterogeneous set of tight junction genes were found to be altered in small and large intestines of adults with IBS, but these have not been evaluated in children. Positive associations were identified between barrier dysfunction and bowel disturbances (6/9 studies), abdominal pain (9/13 studies), overall symptom severity (1/6 studies), depression and anxiety (1/1 study) and quality of life (1/4 studies). Fecal slurry or supernatants of IBS patients were found to induce barrier disruption in animal models (5/6 studies). Conclusions: Barrier dysfunction is present in a significant proportion of adult and all pediatric IBS studies, especially in the IBS-D and PI-IBS subtype. The majority of studies indicated a positive association between loss of barrier function and symptoms such as abdominal pain and changes in the bowel function.

Published:

February 24, 2021

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Title:

Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease

Authors:

Phillips, Matthew C. L.; Deprez, Laura M.; Mortimer, Grace M. N.; Murtagh, Deborah K. J.; McCoy, Stacey; Mylchreest, Ruth; Gilbertson, Linda J.; Clark, Karen M.; Simpson, Patricia V.; McManus, Eileen J.; Oh, Jee-Eun; Yadavaraj, Satish; King, Vanessa M.; Pillai, Avinesh; Romero-Ferrando, Beatriz; Brinkhuis, Martijn; Copeland, Bronwyn M.; Samad, Shah; Liao, Shenyang; Schepel, Jan A. C.

Abstract:

Brain energy metabolism is impaired in Alzheimer’s disease (AD), which may be mitigated by a ketogenic diet. We conducted a randomized crossover trial to determine whether a 12-week modified ketogenic diet improved cognition, daily function, or quality of life in a hospital clinic of AD patients.

Published:

February 23, 2021

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Title:

Evolutionary development of the Homo antecessor scapulae (Gran Dolina site, Atapuerca) suggests a modern-like development for Lower Pleistocene Homo

Authors:

García-Martínez, Daniel; Green, David J.; Bermúdez de Castro, José María

Abstract:

Two well-preserved, subadult 800 ky scapulae from Gran Dolina belonging to Homo antecessor, provide a unique opportunity to investigate the ontogeny of shoulder morphology in Lower Pleistocene humans. We compared the H. antecessor scapulae with a sample of 98 P. troglodytes and 108 H. sapiens representatives covering seven growth stages, as well as with the DIK-1-1 (Dikika; Australopithecus afarensis), KNM-WT 15000 (Nariokotome; H. ergaster), and MH2 (Malapa; A. sediba) specimens. We quantified 15 landmarks on each scapula and performed geometric morphometric analyses. H. sapiens scapulae are mediolaterally broader with laterally oriented glenoid fossae relative to Pan and Dikika shoulder blades. Accordingly, H. antecessor scapulae shared more morphological affinities with modern humans, KNM-WT 15000, and even MH2. Both H. antecessor and modern Homo showed significantly more positive scapular growth trajectories than Pan (slopes: P. troglodytes = 0.0012; H. sapiens = 0.0018; H. antecessor = 0.0020). Similarities in ontogenetic trajectories between the H. antecessor and modern human data suggest that Lower Pleistocene hominin scapular development was already modern human-like. At the same time, several morphological features distinguish H. antecessor scapulae from modern humans along the entire trajectory. Future studies should include additional Australopithecus specimens for further comparative assessment of scapular growth trends.

Published:

February 18, 2021

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Title:

Lactate augments intramuscular triglyceride accumulation and mitochondrial biogenesis in rats

Authors:

Zhou, L.; Chen, S. Y.; Han, H. J.; Sun, J. Q.

Abstract:

Regular exercise induces intramuscular triglyceride accumulation with improved mitochondrial ability, but the mechanism remains unknown. The glycolytic product of exercise, lactate, has long been rec-ognized to suppress lipolysis and promote lipogenesis in adipocytes through inhibition of the cAMP-PKA pathway by activation of the G protein-coupled receptor (GPR81). However, whether lactate results in a similar process in skeletal muscle is unclear. Here, by using intramuscular injection of lactate to the gastrocnemius, the lipid metabolism effects were investigated in rat skeletal muscle. Firstly, the lactate-injection effect was verified by comparing changes in blood lactate levels from injection and exercise (30 min, 31 m/min, treadmill running). After five weeks of lactate intervention, intramuscular triglyceride levels in the gastrocnemius and the proportion of epididymis adipose mass to body weight increased. Chronic intramuscular injection of lactate elevated lactate receptor, GPR81, and reduced cAMP response element-binding (CREB) and P-CREB abundance in the gastrocnemius. Additionally, there was a significant decline in lipolytic-related proteins (AMPK, P-AMPK, P-HSL, CPT-1B, TGF-β2, SDHA) and a significant increase in fat synthesis proteins (SREBP-1C, PPAR-γ). Surprisingly, mitochondrial biomarkers (PGC-1α, CS) were also increased in the gastrocnemius, suggesting that chronic lactate might promote mitochondria biogenesis. Together, these results demonstrated that lactate may play a crucial role in triglyceride storage and mitochondria biogenesis in the skeletal muscle of rat.

Published:

February 17, 2021

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Title:

Climate change, not human population growth, correlates with Late Quaternary megafauna declines in North America

Authors:

Stewart, Mathew; Carleton, W. Christopher; Groucutt, Huw S.

Abstract:

The disappearance of many North American megafauna at the end of the Pleistocene is a contentious topic. While the proposed causes for megafaunal extinction are varied, most researchers fall into three broad camps emphasizing human overhunting, climate change, or some combination of the two. Understanding the cause of megafaunal extinctions requires the analysis of through-time relationships between climate change and megafauna and human population dynamics. To do so, many researchers have used summed probability density functions (SPDFs) as a proxy for through-time fluctuations in human and megafauna population sizes. SPDFs, however, conflate process variation with the chronological uncertainty inherent in radiocarbon dates. Recently, a new Bayesian regression technique was developed that overcomes this problem—Radiocarbon-dated Event-Count (REC) Modelling. Here we employ REC models to test whether declines in North American megafauna species could be best explained by climate changes, increases in human population densities, or both, using the largest available database of megafauna and human radiocarbon dates. Our results suggest that there is currently no evidence for a persistent through-time relationship between human and megafauna population levels in North America. There is, however, evidence that decreases in global temperature correlated with megafauna population declines.

Published:

February 16, 2021

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Title:

A Concise Review of Ketogenic Dietary Interventions in the Management of Rare Diseases

Authors:

Hettiarachchi, D.; Lakmal, K.; Dissanayake, V. H. W.

Abstract:

Dietary interventions are now being used as an adjunct therapy in the treatment of rare diseases. One such method is the high-fat, moderate-protein, and very low-carbohydrate diet which produces ketosis and therefore called the ketogenic diet. Some of the more common conditions that are treated with this method are pharmacoresistant epilepsy, infantile spasms, glycogen storage diseases, and other forms of rare metabolic disturbances. With this review, we look at different uses of the ketogenic diet in treating rare diseases and the recommendations based on current evidence.

Published:

February 15, 2021

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Title:

Dietary Diversification and Specialisation in New World Bats Facilitated by Early Molecular Evolution

Authors:

Potter, Joshua H. T.; Davies, Kalina T. J.; Yohe, Laurel R.; Sanchez, Miluska K. R.; Rengifo, Edgardo M.; Struebig, Monika; Warren, Kim; Tsagkogeorga, Georgia; Lim, Burton K.; Dos Reis, Mario; Dávalos, Liliana M.; Rossiter, Stephen J.

Abstract:

Dietary adaptation is a major feature of phenotypic and ecological diversification, yet the genetic basis of dietary shifts is poorly understood. Among mammals, Neotropical leaf-nosed bats (family Phyllostomidae) show unmatched diversity in diet; from a putative insectivorous ancestor, phyllostomids have radiated to specialize on diverse food sources, including blood, nectar, and fruit. To assess whether dietary diversification in this group was accompanied by molecular adaptations for changing metabolic demands, we sequenced 89 transcriptomes across 58 species, and combined these with published data to compare ∼13,000 protein coding genes across 66 species. We tested for positive selection on focal lineages, including those inferred to have undergone dietary shifts. Unexpectedly, we found a broad signature of positive selection in the ancestral phyllostomid branch, spanning genes implicated in the metabolism of all major macronutrients, yet few positively selected genes at the inferred switch to plantivory. Branches corresponding to blood- and nectar-based diets showed selection in loci underpinning nitrogenous waste excretion and glycolysis, respectively. Intriguingly, patterns of selection in metabolism genes were mirrored by those in loci implicated in craniofacial remodelling, a trait previously linked to phyllostomid dietary specialisation. Finally, using simulations, we show that the widely-used branch-site model is likely to be misspecified, with the implication that it is too conservative and probably under-reports true cases of positive selection. Our findings point to a complex picture of adaptive radiation, in which the evolution of new dietary specialisations has been facilitated by early adaptations combined with the generation of new genetic variation.

Published:

February 15, 2021

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Title:

Use of glycated albumin for the identification of diabetes in subjects from northeast China

Authors:

Li, Guo-Yan; Li, Hao-Yu; Li, Qiang

Abstract:

BACKGROUND: Metabolic memory is important for the diagnosis and treatment of diabetes in the early stage, and in maintaining blood glucose concentrations within the normal range. The clinical diagnosis of diabetes mellitus is currently made using fasting plasma glucose, 2 h-plasma glucose (2h-PG) during a 75 g oral glucose tolerance test, and hemoglobin A1c (HbA1c) level. However, the fasting plasma glucose test requires fasting, which is a barrier to screening, and reproducibility of the 2h-PG level is poor. HbA1c is affected by a shortened red blood cell lifespan. In patients with anemia and hemoglobinopathies, the measured HbA1c levels may be inaccurate. Compared with HbA1c, glycated albumin (GA) is characterized by more rapid and greater changes, and can be used to diagnose new-onset diabetes especially if urgent early treatment is required, for example in gestational diabetes. In this study, we provided cutoff values for GA and evaluated its utility as a screening and diagnostic tool for diabetes in a large high-risk group study. AIM: To evaluate the utility of GA in identifying subjects with diabetes in northeast China, and to assess the diagnostic accuracy of the proposed GA cutoff in the diagnosis of diabetes mellitus. METHODS: This cross-sectional study included 1935 subjects, with suspected diabetes or in high-risk groups, from 2014 to 2015 in the Second Affiliated Hospital of Harbin Medical University (Harbin, China). The use of GA to identify diabetes was investigated using the area under the receiver operating characteristic curve (AUC). The GA cutoffs were derived from different 2h-PG values with hemoglobin A1c cutoffs used as a calibration curve. RESULTS: The GA cutoff for the diagnosis of diabetes mellitus was 15.15% from the receiver operating characteristic (ROC) curve. ROC analysis demonstrated that GA was an efficient marker for detecting diabetes, with an AUC of 90.3%. CONCLUSION: Our study supports the use of GA as a biomarker for the diagnosis of diabetes.

Published:

February 15, 2021

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Title:

The fat storage system

Authors:

Abstract:

Perhaps not a very sexy name but why name it something else than what it is? After studying the functioning of our lipoproteins for a good 2 years (and still not finished learning!), it has finally…

Published:

February 14, 2021

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Title:

Major royal jelly proteins prevents NAFLD by improving mitochondrial function and lipid accumulation through activating the AMPK / SIRT3 pathway in vitro

Authors:

Zhang, Xiaochen; Lu, Xinyang; Zhou, Yingjun; Guo, Xinyu; Chang, Yaning

Abstract:

Nonalcoholic fatty liver disease (NAFLD) is a metabolic syndrome, whose main characteristics are excessive lipid accumulation and oxidative stress. Major royal jelly proteins (MRJPs) is a kind of water-soluble protein, which is abundant in royal jelly (RJ). The aim of this study was to evaluate the effect of MRJPs on lipid accumulation and oxidative stress of liver cells. Here, we first optimized the conditions for extracting MRJPs from RJ and identified the extraction effect and product by SDS-PAGE. Then, we used oleic acid (OA) of 1.0 mM to induce hepatocytes for 24 hr to establish a stable cell models of lipid accumulation, and we found that pre-administration (24 hr) of MRJPs (0.2, 0.5, and 1.0 g/L) could significantly reduce the lipid drop content and triglyceride level in the model cells, and simultaneously reduce the alanine aminotransferase and aspertate aminotransferase levels in the cell culture supernatant. In addition, pre-incubation (24 hr) with MRJPs (0.2, 0.5, and 1.0 g/L) could restore superoxide dismutase (SOD) level and mitochondrial membrane potential as compared with OA group. Furthermore, MRJPs administration significantly upregulated the expression of Silent Information Regulator 2 Associated Protein 3, mitochondrial superoxide dismutase (SOD2), and cytochrome c oxidase subunit IV in OA-treated HepG2 cells. The study for the first time provides evidences on the lipid-lowering effect of MRJPs at the cellular level, which can further provide support for the development and application of polypeptide drugs in the future, and can also provide a choice for the prevention and treatment of liver metabolic diseases represented by NAFLD. PRACTICAL APPLICATION: Our study proved that MRJPs had substantial preventing effect on OA-induced lipid accumulation and mitochondrial dysfunction in HepG2 cells. This research can further provide theoretical support for the development and application of peptide drugs in the future. Besides, it can not only further broaden our understanding of NAFLD and other diseases, but also provide ideas for research on oxidative stress and lipid accumulation in the body.

Published:

February 13, 2021

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Title:

Weight loss, hypertension and mental well-being improvements during COVID-19 with a multicomponent health promotion programme on Zoom: a service evaluation in primary care

Authors:

Walker, Louise; Smith, Natalie; Delon, Christine

Abstract:

Background Obesity is a risk factor for complications from SARS-CoV-2 infection, increasing the need for effective weight management measures in primary care. However, in the UK, COVID-19 restrictions have hampered primary care weight management referral and delivery, and COVID-19 related weight gain has been reported. The present study evaluated outcomes from a multicomponent weight loss and health promotion programme in UK primary care, delivered remotely due to COVID-19 restrictions. Method Patients with obesity, type 2 diabetes or pre-diabetes attended six 90 min sessions over 10 weeks on Zoom. The dietary component comprised a low-carbohydrate ‘real food’ approach, augmented with education on physical activity, intermittent fasting, gut health, stress management, sleep and behaviour change. Anthropometric and cardiometabolic data were self-reported. Mental well-being was assessed with the Warwick Edinburgh Mental Wellbeing Scale. Subjective outcomes and participant feedback about the programme were collected with an anonymous online survey. Results Twenty participants completed the programme. Weight loss and improvements in body mass index, waist circumference, systolic and diastolic blood pressure and mental well-being achieved statistical and clinical significance. Mean weight loss (5.8 kg) represented a 6.5% weight loss. Participants’ subjective outcomes included weight loss without hunger (67%) and increased confidence in their ability to improve health (83%). All participants reported the usage of Zoom to access the programme as acceptable with 83% reporting it worked well. Conclusion A multicomponent weight loss and health promotion programme with a low-carbohydrate dietary component, clinically and statistically significantly improved health outcomes including weight status, blood pressure and mental well-being in a group of primary care patients when delivered remotely. Further research is warranted.

Published:

February 13, 2021

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Title:

Grading fecal consistency in an omnivorous carnivore, the brown bear: Abandoning the concept of uniform feces

Authors:

De Cuyper, Annelies; Clauss, Marcus; Lens, Luc; Strubbe, Diederik; Zedrosser, Andreas; Steyaert, Sam; Saravia, Arturo Muñoz; Janssens, Geert P. J.

Abstract:

Grading the fecal consistency of carnivores is a frequently used tool for monitoring gut health and overall digestion. Several fecal consistency grading systems are available for mainly felids and canids. No such system exists for the brown bear (Ursus arctos Linnaeus, 1758). We aim at extending current fecal consistency grading systems with a scoring system for brown bears. The system was set up during a diet study with nine individuals fed a variety of diets including beef meat, rabbit, fruit, and grass-fruit-pellet mix in an incomplete crossover design. One additional individual was included opportunistically and was fed the typical zoo diet (vegetable-fruit-meat-pellet diet). All feces from the collection period were photographed, graded by "handling the feces" and visually inspected for dietary components. Based on a total of 446 feces, a six-point scale for uniform fecal consistencies was established. In 11% of all feces, two distinct consistencies could be distinguished, a feature that appears in other carnivore species as well. Hence, an additional grading system for dual consistencies was developed. The fecal consistency of brown bears is heavily dependent on the diet items processed before defecation with the general observation that the more vegetation or whole prey, the firmer the feces, and at certain proportions of the latter, the higher the chance for dual fecal consistencies to occur. The results indicate that in bears, diet may have a strong effect on fecal consistency, hampering animal health assessments without prior knowledge of the diet.

Published:

February 12, 2021

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Title:

A High-Fat Diet Induces Lower Systemic Inflammation than a High-Carbohydrate Diet in Mice

Authors:

de Almeida-Souza, Camila B.; Antunes, Marina M.; Carbonera, Fabiana; Godoy, Guilherme; da Silva, Maria A. R. C. P.; Masi, Laureane N.; Visentainer, Jesui V.; Curi, Rui; Bazotte, Roberto B.

Abstract:

Background: We previously established that male Swiss mice (Mus musculus) receiving a high-fat diet (HFD) during 8 weeks exhibit similar caloric ingestion and body weight (grams) compared with mice fed a high-carbohydrate diet (HCD). HFD mice exhibit a lower inflammatory state than an HCD in the liver, skeletal muscle, and brain. In addition, we demonstrated that HFD and HCD modulated fatty acids (FA) composition in these tissues. In this study, our objective was to compare HFD mice and HCD mice in terms of systemic inflammation. Methods: Saturated FA (SFA), monounsaturated FA, omega-6 polyunsaturated FA (n-6 PUFA), and n-3 PUFA were evaluated at the time points 0, 1, 7, 14, 28, and 56 days after starting the administration of the diets. We investigated n-6 PUFA:n-3 PUFA, SFA:n-3 PUFA, palmitic acid:α-linolenic acid (ALA), and myristic acid:docosahexaenoic acid (DHA) ratios as potential serum biomarkers of systemic inflammation. We also measured the serum levels of basic fibroblast growth factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), inducible protein 10 (IP-10), interferon gamma (IFN-γ), interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, macrophage inflammatory protein-1α (MIP-1-α), monocyte chemotactic protein 1 (MCP-1), monokine induced by IFN-γ (MIG), and tumor necrosis factor α (TNF-α). Results: The HFD group had lower (P 

Published:

February 10, 2021

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Title:

A High-Fat Diet Induces Lower Systemic Inflammation than a High-Carbohydrate Diet in Mice

Authors:

de Almeida-Souza, Camila B.; Antunes, Marina M.; Carbonera, Fabiana; Godoy, Guilherme; da Silva, Maria A. R. C. P.; Masi, Laureane N.; Visentainer, Jesui V.; Curi, Rui; Bazotte, Roberto B.

Abstract:

Background: We previously established that male Swiss mice (Mus musculus) receiving a high-fat diet (HFD) during 8 weeks exhibit similar caloric ingestion and body weight (grams) compared with mice fed a high-carbohydrate diet (HCD). HFD mice exhibit a lower inflammatory state than an HCD in the liver, skeletal muscle, and brain. In addition, we demonstrated that HFD and HCD modulated fatty acids (FA) composition in these tissues. In this study, our objective was to compare HFD mice and HCD mice in terms of systemic inflammation. Methods: Saturated FA (SFA), monounsaturated FA, omega-6 polyunsaturated FA (n-6 PUFA), and n-3 PUFA were evaluated at the time points 0, 1, 7, 14, 28, and 56 days after starting the administration of the diets. We investigated n-6 PUFA:n-3 PUFA, SFA:n-3 PUFA, palmitic acid:α-linolenic acid (ALA), and myristic acid:docosahexaenoic acid (DHA) ratios as potential serum biomarkers of systemic inflammation. We also measured the serum levels of basic fibroblast growth factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), inducible protein 10 (IP-10), interferon gamma (IFN-γ), interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, macrophage inflammatory protein-1α (MIP-1-α), monocyte chemotactic protein 1 (MCP-1), monokine induced by IFN-γ (MIG), and tumor necrosis factor α (TNF-α). Results: The HFD group had lower (P 

Published:

February 10, 2021

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Title:

Carbohydrate restriction following strenuous glycogen-depleting exercise does not potentiate the acute molecular response associated with mitochondrial biogenesis in human skeletal muscle

Authors:

Ramos, Catarina; Cheng, Arthur J.; Kamandulis, Sigitas; Subocius, Andrejus; Brazaitis, Marius; Venckunas, Tomas; Chaillou, Thomas

Abstract:

PURPOSE: Carbohydrate (CHO) restriction could be a potent metabolic regulator of endurance exercise-induced muscle adaptations. Here, we determined whether post-exercise CHO restriction following strenuous exercise combining continuous cycling exercise (CCE) and sprint interval exercise could affect the gene expression related to mitochondrial biogenesis and oxidative metabolism in human skeletal muscle. METHODS: In a randomized cross-over design, 8 recreationally active males performed two cycling exercise sessions separated by 4 weeks. Each session consisted of 60-min CCE and six 30-s all-out sprints, which was followed by ingestion of either a CHO or placebo beverage in the post-exercise recovery period. Muscle glycogen concentration and the mRNA levels of several genes related to mitochondrial biogenesis and oxidative metabolism were determined before, immediately after, and at 3 h after exercise. RESULTS: Compared to pre-exercise, strenuous cycling led to a severe muscle glycogen depletion (> 90%) and induced a large increase in PGC1A and PDK4 mRNA levels (~ 20-fold and ~ 10-fold, respectively) during the acute recovery period in both trials. The abundance of the other transcripts was not changed or was only moderately increased during this period. CHO restriction during the 3-h post-exercise period blunted muscle glycogen resynthesis but did not increase the mRNA levels of genes associated with muscle adaptation to endurance exercise, as compared with abundant post-exercise CHO consumption. CONCLUSION: CHO restriction after a glycogen-depleting and metabolically-demanding cycling session is not effective for increasing the acute mRNA levels of genes involved in mitochondrial biogenesis and oxidative metabolism in human skeletal muscle.

Published:

February 10, 2021

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Title:

Acute Nutritional Ketosis and Its Implications for Plasma Glucose and Glucoregulatory Peptides in Adults with Prediabetes: A Crossover Placebo-Controlled Randomized Trial

Authors:

Bharmal, Sakina H.; Cho, Jaelim; C Alarcon Ramos, Gisselle; Ko, Juyeon; Cameron-Smith, David; Petrov, Maxim S.

Abstract:

BACKGROUND: The potential of a ketone monoester (β-hydroxybutyrate; KEβHB) supplement to rapidly mimic a state of nutritional ketosis offers a new therapeutic possibility for diabetes prevention and management. While KEβHB supplementation has a glucose-lowering effect in adults with obesity, its impact on glucose control in other insulin-resistant states is unknown. OBJECTIVES: The primary objective was to investigate the effect of KEβHB-supplemented drink on plasma glucose in adults with prediabetes. The secondary objective was to determine its impact on plasma glucoregulatory peptides. METHODS: This randomized controlled trial [called CETUS (Cross-over randomizEd Trial of β-hydroxybUtyrate in prediabeteS)] included 18 adults [67% men, mean age = 55 y, mean BMI (kg/m2) = 28.4] with prediabetes (glycated hemoglobin between 5.7% and 6.4% and/or fasting plasma glucose between 100 and 125 mg/dL). Participants were randomly assigned to receive KEβHB-supplemented and placebo drinks in a crossover sequence (washout period of 7-10 d between the drinks). Blood samples were collected from 0 to 150 min, at intervals of 30 min. Paired-samples t tests were used to investigate the change in the outcome variables [β-hydroxybutyrate (βHB), glucose, and glucoregulatory peptides] after both drinks. Repeated measures analyses were conducted to determine the change in concentrations of the prespecified outcomes over time. RESULTS: Blood βHB concentrations increased to 3.5 mmol/L within 30 minutes after KEβHB supplementation. Plasma glucose AUC was significantly lower after KEβHB supplementation than after the placebo [mean difference (95% CI): -59 (-85.3, -32.3) mmol/L × min]. Compared with the placebo, KEβHB supplementation led to significantly greater AUCs for plasma insulin [0.237 (0.044, 0.429) nmol/L × min], C-peptide [0.259 (0.114, 0.403) nmol/L × min], and glucose-dependent insulinotropic peptide [0.243 (0.085, 0.401) nmol/L × min], with no significant differences in the AUCs for amylin, glucagon, and glucagon-like peptide 1. CONCLUSIONS: Ingestion of the KEβHB-supplemented drink acutely increased the blood βHB concentrations and lowered the plasma glucose concentrations in adults with prediabetes. Further research is needed to investigate the dynamics of repeated ingestions of a KEβHB supplement by individuals with prediabetes, with a view to preventing new-onset diabetes. This trial was registered at www.clinicaltrials.gov as NCT03889210.

Published:

February 9, 2021

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Title:

Carbohydrate-Restricted Diet: A Successful Strategy for Short-Term Management in Youth with Severe Obesity-An Observational Study

Authors:

Pauley, Meghan; Mays, Chadd; Bailes, James R.; Schwartzman, Michal Laniado; Castle, Mark; McCoy, Marji; Patick, Casey; Preston, Deborah; Nudelman, Matthew J. R.; Denning, Krista L.; Bellner, Lars; Werthammer, Joseph

Abstract:

Background: Obesity affects ∼20% of children in the United States and reports of successful dietary treatment are lacking. This study aimed to determine the change in body weight in severely obese youth after carbohydrate-restricted dietary intervention. Methods: This single-center study of a carbohydrate-restricted diet (≤30 grams per day), with unlimited calories, fat, and protein for 3-4 months, examined two groups of severely obese youth of ages 5-18 years: Group A, retrospectively reviewed charts of severely obese youth referred to the Pediatric Obesity Clinic at Hoops Family Children's Hospital and the Ambulatory Division of Marshall Pediatrics, Marshall University School of Medicine, in Huntington, WV, between July 1, 2014 and June 30, 2017 (n = 130), and Group B, prospective participants, referred between July 1, 2018 and December 31, 2018, followed with laboratory studies pre- and postdietary intervention (n = 8). Results: In Group A, 310 participants began the diet, 130 (42%) returned after 3-4 months. Group B had 14 enrollees who began the diet, and 8 followed up at 3-4 months (57%). Girls compared with boys were more likely to complete the diet (P = 0.02). Participants <12 years age were almost twice as likely to complete the diet compared with those 12-18 years (64% vs. 36%, P < 0.01); however, the older group subjects who completed the diet had the same percentage of weight loss compared with those <12 years (6.9% vs. 6.9%). Group A had reductions in weight of 5.1 kg (P < 0.001), body mass index (BMI) 2.5 kg/m2 (P < 0.001), and percentage weight loss 6.9% (P < 0.001). Group B had reductions in weight 9.6 kg (P < 0.01), BMI 4 kg/m2 (P < 0.01), and percentage weight loss 9% (P < 0.01). In addition, participants had significant reductions of fasting serum insulin (P < 0.01), triglycerides (P < 0.01), and 20-hydroxyeicosatetraenoic acid (P 

Published:

February 9, 2021

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Title:

Dog domestication and the dual dispersal of people and dogs into the Americas

Authors:

Perri, Angela R.; Feuerborn, Tatiana R.; Frantz, Laurent A. F.; Larson, Greger; Malhi, Ripan S.; Meltzer, David J.; Witt, Kelsey E.

Abstract:

Advances in the isolation and sequencing of ancient DNA have begun to reveal the population histories of both people and dogs. Over the last 10,000 y, the genetic signatures of ancient dog remains have been linked with known human dispersals in regions ...

Published:

February 9, 2021

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Title:

Egg and cholesterol consumption and mortality from cardiovascular and different causes in the United States: A population-based cohort study

Authors:

Zhuang, Pan; Wu, Fei; Mao, Lei; Zhu, Fanghuan; Zhang, Yiju; Chen, Xiaoqian; Jiao, Jingjing; Zhang, Yu

Abstract:

Background Whether consumption of egg and cholesterol is detrimental to cardiovascular health and longevity is highly debated. Data from large-scale cohort studies are scarce. This study aimed to examine the associations of egg and cholesterol intakes with mortality from all causes, cardiovascular disease (CVD), and other causes in a US population. Methods and findings Overall, 521,120 participants (aged 50–71 years, mean age = 62.2 years, 41.2% women, and 91.8% non-Hispanic white) were recruited from 6 states and 2 additional cities in the US between 1995 and 1996 and prospectively followed up until the end of 2011. Intakes of whole eggs, egg whites/substitutes, and cholesterol were assessed by a validated food frequency questionnaire. Cause-specific hazard models considering competing risks were used, with the lowest quintile of energy-adjusted intake (per 2,000 kcal per day) as the reference. There were 129,328 deaths including 38,747 deaths from CVD during a median follow-up of 16 years. Whole egg and cholesterol intakes were both positively associated with all-cause, CVD, and cancer mortality. In multivariable-adjusted models, the hazard ratios (95% confidence intervals) associated with each intake of an additional half of a whole egg per day were 1.07 (1.06–1.08) for all-cause mortality, 1.07 (1.06–1.09) for CVD mortality, and 1.07 (1.06–1.09) for cancer mortality. Each intake of an additional 300 mg of dietary cholesterol per day was associated with 19%, 16%, and 24% higher all-cause, CVD, and cancer mortality, respectively. Mediation models estimated that cholesterol intake contributed to 63.2% (95% CI 49.6%–75.0%), 62.3% (95% CI 39.5%–80.7%), and 49.6% (95% CI 31.9%–67.4%) of all-cause, CVD, and cancer mortality associated with whole egg consumption, respectively. Egg white/substitute consumers had lower all-cause mortality and mortality from stroke, cancer, respiratory disease, and Alzheimer disease compared with non-consumers. Hypothetically, replacing half a whole egg with equivalent amounts of egg whites/substitutes, poultry, fish, dairy products, or nuts/legumes was related to lower all-cause, CVD, cancer, and respiratory disease mortality. Study limitations include its observational nature, reliance on participant self-report, and residual confounding despite extensive adjustment for acknowledged dietary and lifestyle risk factors. Conclusions In this study, intakes of eggs and cholesterol were associated with higher all-cause, CVD, and cancer mortality. The increased mortality associated with egg consumption was largely influenced by cholesterol intake. Our findings suggest limiting cholesterol intake and replacing whole eggs with egg whites/substitutes or other alternative protein sources for facilitating cardiovascular health and long-term survival. Trial registration ClinicalTrials.gov NCT00340015.

Published:

February 9, 2021

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Title:

Maternal Intake of Dietary Fat Pre-programs Offspring's Gut Ecosystem Altering Colonization Resistance and Immunity to Infectious Colitis in Mice

Authors:

Quin, Candice; Ghosh, Sanjoy; Dai, Chuanbin; Barnett, Jacqueline A.; Garner, Alexander M.; Yoo, Rachael K. H.; Zandberg, Wesley F.; Botta, Amy; Gorzelak, Monika; Gibson, Deanna L.

Abstract:

SCOPE: The transgenerational impact of dietary fat remains unclear. Here, the role of maternal fat consumption as a modulator of gut microbial communities and infectious disease outcomes in their offspring is explored. METHODS AND RESULTS: C57BL/6 mice were fed isocaloric high-fat diets throughout breeding, gestation and lactation. Diets contained either milk fat (MF), olive oil (OO) or corn oil (CO), with or without fish oil. The pups born to maternally exposed mice were weaned on to chow and raised into adulthood. At 8 weeks, the offspring were either euthanized for colonic 16S rRNA analysis or challenged with the enteric pathogen, Citrobacter rodentium. Maternal CO exposure resulted in unique clustering of bacterial communities in offspring compared with MF and OO. Diets rich in CO reduced survival in offspring challenged with C. rodentium. The addition of fish oil did not improve mortality caused by CO and worsened disease outcomes when combined with OO. Unlike the unsaturated diets, MF was protective with and without fish oil. CONCLUSIONS: Overall, these data reveal that maternal intake of fatty acids do have transgenerational impacts on their offspring's bacteriome and enteric infection risk.Based on this study, saturated fats should be included in maternal diets. This article is protected by copyright. All rights reserved.

Published:

February 9, 2021

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Title:

Maternal Intake of Dietary Fat Pre-programs Offspring's Gut Ecosystem Altering Colonization Resistance and Immunity to Infectious Colitis in Mice

Authors:

Quin, Candice; Ghosh, Sanjoy; Dai, Chuanbin; Barnett, Jacqueline A.; Garner, Alexander M.; Yoo, Rachael K. H.; Zandberg, Wesley F.; Botta, Amy; Gorzelak, Monika; Gibson, Deanna L.

Abstract:

SCOPE: The transgenerational impact of dietary fat remains unclear. Here, the role of maternal fat consumption as a modulator of gut microbial communities and infectious disease outcomes in their offspring is explored. METHODS AND RESULTS: C57BL/6 mice were fed isocaloric high-fat diets throughout breeding, gestation and lactation. Diets contained either milk fat (MF), olive oil (OO) or corn oil (CO), with or without fish oil. The pups born to maternally exposed mice were weaned on to chow and raised into adulthood. At 8 weeks, the offspring were either euthanized for colonic 16S rRNA analysis or challenged with the enteric pathogen, Citrobacter rodentium. Maternal CO exposure resulted in unique clustering of bacterial communities in offspring compared with MF and OO. Diets rich in CO reduced survival in offspring challenged with C. rodentium. The addition of fish oil did not improve mortality caused by CO and worsened disease outcomes when combined with OO. Unlike the unsaturated diets, MF was protective with and without fish oil. CONCLUSIONS: Overall, these data reveal that maternal intake of fatty acids do have transgenerational impacts on their offspring's bacteriome and enteric infection risk.Based on this study, saturated fats should be included in maternal diets. This article is protected by copyright. All rights reserved.

Published:

February 9, 2021

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Title:

The Southern European Atlantic Diet and all-cause mortality in older adults

Authors:

Carballo-Casla, Adrián; Ortolá, Rosario; García-Esquinas, Esther; Oliveira, Andreia; Sotos-Prieto, Mercedes; Lopes, Carla; Lopez-Garcia, Esther; Rodríguez-Artalejo, Fernando

Abstract:

The Southern European Atlantic Diet (SEAD) is the traditional diet of Northern Portugal and North-Western Spain. Higher adherence to the SEAD has been associated with lower levels of some cardiovascular risk factors and reduced risk for myocardial infarction, but whether this translates into lower all-cause mortality is uncertain. We hence examined the association between adherence to the SEAD and all-cause mortality in older adults.

Published:

February 9, 2021

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Title:

Plasma acylcarnitines and risk of lower-extremity functional impairment in older adults: a nested case-control study

Authors:

Caballero, Francisco Félix; Struijk, Ellen A.; Lana, Alberto; Buño, Antonio; Rodríguez-Artalejo, Fernando; Lopez-Garcia, Esther

Abstract:

Elevated concentrations of acylcarnitines have been associated with higher risk of obesity, type 2 diabetes and cardiovascular disease. The aim of the present study was to assess the association between L-carnitine and acylcarnitine profiles, and 2-year risk of incident lower-extremity functional impairment (LEFI). This case-control study is nested in the Seniors-ENRICA cohort of community-dwelling older adults, which included 43 incident cases of LEFI and 86 age- and sex- matched controls. LEFI was assessed with the Short Physical Performance Battery. Plasma L-carnitine and 28 acylcarnitine species were measured. After adjusting for potential confounders, medium-chain acylcarnitines levels were associated with 2-year incidence of LEFI [odds ratio per 1-SD increase: 1.69; 95% confidence interval: 1.08, 2.64; p = 0.02]. Similar results were observed for long-chain acylcarnitines [odds ratio per 1-SD increase: 1.70; 95% confidence interval: 1.03, 2.80; p = 0.04]. Stratified analyses showed a stronger association between medium- and long-chain acylcarnitines and incidence of LEFI among those with body mass index and energy intake below the median value. In conclusion, higher plasma concentrations of medium- and long-chain acylcarnitines were associated with higher risk of LEFI. Given the role of these molecules on mitochondrial transport of fatty acids, our results suggest that bioenergetics dysbalance contributes to LEFI.

Published:

February 8, 2021

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Title:

New model could explain old cholesterol mystery

Authors:

Spilde, Ingrid

Abstract:

Saturated fats increase cholesterol. And high cholesterol is linked to heart disease. But why are researchers unable to show that saturated fat actually leads to heart disease?

Published:

February 7, 2021

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Title:

Vegan diet in young children remodels metabolism and challenges the statuses of essential nutrients

Authors:

Hovinen, Topi; Korkalo, Liisa; Freese, Riitta; Skaffari, Essi; Isohanni, Pirjo; Niemi, Mikko; Nevalainen, Jaakko; Gylling, Helena; Zamboni, Nicola; Erkkola, Maijaliisa; Suomalainen, Anu

Abstract:

Abstract Vegan diets are gaining popularity, also in families with young children. However, the effects of strict plant-based diets on metabolism and micronutrient status of children are unknown. We recruited 40 Finnish children with a median age 3.5 years?vegans, vegetarians, or omnivores from same daycare centers?for a cross-sectional study. They enjoyed nutritionist-planned vegan or omnivore meals in daycare, and the full diets were analyzed with questionnaires and food records. Detailed analysis of serum metabolomics and biomarkers indicated vitamin A insufficiency and border-line sufficient vitamin D in all vegan participants. Their serum total, HDL and LDL cholesterol, essential amino acid, and docosahexaenoic n-3 fatty acid (DHA) levels were markedly low and primary bile acid biosynthesis, and phospholipid balance was distinct from omnivores. Possible combination of low vitamin A and DHA status raise concern for their visual health. Our evidence indicates that (i) vitamin A and D status of vegan children requires special attention; (ii) dietary recommendations for children cannot be extrapolated from adult vegan studies; and (iii) longitudinal studies on infant-onset vegan diets are warranted.

Published:

February 5, 2021

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Title:

A Ketogenic Diet Differentially Affects Neuron And Astrocyte Transcription

Authors:

Koppel, Scott J.; Pei, Dong; Wilkins, Heather M.; Weidling, Ian W.; Wang, Xiaowan; Menta, Blaise W.; Perez-Ortiz, Judit; Kalani, Anuradha; Manley, Sharon; Novikova, Lesya; Koestler, Devin C.; Swerdlow, Russell H.

Abstract:

Ketogenic diets (KDs) alter brain metabolism. Multiple mechanisms may account for their effects, and different brain regions may variably respond. Here, we considered how a KD affects brain neuron and astrocyte transcription. We placed male C57Bl6/N mice on either a 3-month KD or chow diet, generated enriched neuron and astrocyte fractions, and used RNA-Seq to assess transcription. Neurons from KD-treated mice generally showed transcriptional pathway activation while their astrocytes showed a mix of transcriptional pathway suppression and activation. The KD especially affected pathways implicated in mitochondrial and endoplasmic reticulum function, insulin signaling, and inflammation. An unbiased analysis of KD-associated expression changes strongly implicated transcriptional pathways altered in AD, which prompted us to explore in more detail the potential molecular relevance of a KD to AD. Our results indicate a KD differently affects neurons and astrocytes, and provide unbiased evidence that KD-induced brain effects are potentially relevant to neurodegenerative diseases such as AD.

Published:

February 4, 2021

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Title:

Stunning photos of nomadic life in remote Mongolia

Authors:

MailOnline

Abstract:

Italian photographer Michele Martinelli, 41, captured images showing the harsh reality of life for Mongolian nomads. They are one of the worlds last remaining nomadic communities.

Published:

February 4, 2021

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Title:

Neuregulin 1/ErbB4 signaling contributes to the anti-epileptic effects of the ketogenic diet

Authors:

Wang, Jin; Huang, Jie; Li, Yuan-Quan; Yao, Shan; Wu, Cui-Hong; Wang, Ying; Gao, Feng; Xu, Min-Dong; Huang, Guo-Bin; Zhao, Chang-Qin; Wu, Jia-Hui; Zhang, Yun-Long; Jiao, Renjie; Deng, Zi-Hao; Jie, Wei; Li, Hui-Bin; Xuan, Aiguo; Sun, Xiang-Dong

Abstract:

The ketogenic diet (KD) has been recognized as a potentially effective therapy to treat neuropsychiatric diseases, including epilepsy. Previous studies have indicated that KD treatment elevates γ-Amino butyric acid (GABA) levels in both human and murine brains, which presumably contributes to the KD’s anti-seizure effects. However, this has not been systematically investigated at the synaptic level, and the underlying molecular mechanisms remain to be elucidated.

Published:

February 3, 2021

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Title:

Urinary oxidized, but not enzymatic vitamin E metabolites are inversely associated with measures of glucose homeostasis in middle-aged healthy individuals

Authors:

Luo, Jiao; Meulmeester, Fleur L.; Martens, Leon G.; Ashrafi, Nadia; de Mutsert, Renée; Mook-Kanamori, Dennis O.; Rosendaal, Frits R.; Willems van Dijk, Ko; le Cessie, Saskia; Mills, Kevin; Noordam, Raymond; van Heemst, Diana

Abstract:

BACKGROUND & AIMS: Damage induced by lipid peroxidation has been associated with impaired glucose homeostasis. Vitamin E (α-tocopherol, α-TOH) competitively reacts with lipid peroxyl radicals to mitigate oxidative damage, and forms oxidized vitamin E metabolites. Accordingly, we aimed to investigate the associations between α-TOH metabolites (oxidized and enzymatic) in both circulation and urine and measures of glucose homeostasis in the general middle-aged population. METHODS: This cross-sectional study was embedded in the population-based Netherlands Epidemiology of Obesity (NEO) Study. α-TOH metabolites in blood (α-TOH and α-CEHC-SO3) and urine [sulfate (SO3) and glucuronide (GLU) of both α-TLHQ (oxidized) and α-CEHC (enzymatic)] were quantified by liquid chromatography coupled with tandem mass spectrometry (LC/MS-MS). Measures of glucose homeostasis (HOMA-B, HOMA-IR, Insulinogenic index and Matsuda index) were obtained from fasting and postprandial blood samples. Multivariable linear regression analyses were performed to assess the associations of α-TOH metabolites and measures of glucose homeostasis. RESULTS: We included 498 participants (45% men) with mean (SD) age of 55.8 (6.1) years who did not use glucose-lowering medication. While blood α-TOH was not associated with measures of glucose homeostasis, urinary oxidized metabolites (α-TLHQ-SO3/GLU) were associated with HOMA-IR and Matsuda index. For example, a one-SD higher α-TLHQ-SO3 was associated with 0.92 (95% CI: 0.87, 0.97) fold lower HOMA-IR and 1.06 (1.01, 1.11) fold higher Matsuda index, respectively. Similar results were obtained for the urinary α-TLHQ to α-CEHC ratio as a measure of oxidized-over-enzymatic conversion of α-TOH. CONCLUSION: Higher urinary levels of oxidized α-TOH metabolites as well as higher oxidized-to-enzymatic α-TOH metabolite ratio, but not circulating α-TOH or enzymatic metabolites, were associated with lower insulin resistance. Rather than circulating α-TOH, estimates of the conversion of α-TOH might be informative in relation to health and disease.

Published:

February 3, 2021

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Title:

Feed additives as a strategic approach to reduce enteric methane production in cattle: modes of action, effectiveness and safety

Authors:

Honan, M.; Feng, X.; Tricarico, J. M.; Kebreab, E.

Abstract:

Increasing consumer concern in greenhouse-gas (GHG) contributions from cattle is pushing the livestock industry to continue to improve their sustainability goals. As populations increase, particularly in low-income countries, the demand for animal-sourced foods will place further pressure to reduce emission intensity. Enteric methane (CH4) production contributes to most of the GHG from livestock; therefore, it is key to mitigating such emissions. Feed additives have primarily been used to increase animal productivity, but advances in understanding the rumen has resulted in their development to mitigate CH4 emissions. The present study reviewed some of the main feed additives with a potential to reduce enteric CH4 emissions, focusing on in vivo studies. Feed additives work by either inhibiting methanogenesis or modifying the rumen environment, such that CH4 production (g/day) is reduced. Feed additives that inhibit methanogenesis or compete with substrate for methanogens include 3-nitroxypropanol (3NOP), nitrates, and halogenated compounds containing organisms such as macroalgae. Although 3NOP and macroalgae affect methyl–coenzyme M reductase enzyme that is necessary in CH4 biosynthesis, the former is more specific to methanogens. In contrast, nitrates reduce CH4 emissions by competing with methanogens for hydrogen. However, nitrite could accumulate in blood and be toxic to ruminants. Rumen modifiers do not act directly on methanogens but rather on the conditions that promote methanogenesis. These feed additives include lipids, plant secondary compounds and essential oils. The efficacy of lipids has been studied extensively, and although supplementation with medium-chain and polyunsaturated fatty acids has shown substantial reduction in enteric CH4 production, the results have been variable. Similarly, secondary plant compounds and essential oils have shown inconsistent results, ranging from substantial reduction to modest increase in enteric CH4 emissions. Due to continued interest in this area, research is expected to accelerate in developing feed additives that can provide options in mitigating enteric CH4 emissions.

Published:

February 2, 2021

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