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Title:
The Impact of Carbohydrate Quality on Dental Plaque pH: Does the Glycemic Index of Starchy Foods Matter for Dental Health?
Authors:
Atkinson, Fiona S.; Khan, Jouhrah Hussain; Brand-Miller, Jennie C.; Eberhard, Joerg
Abstract:
Sugary carbohydrate foods have long been associated with increased risk of dental caries formation, but the dental health impact of starchy carbohydrates, particularly those with a high glycemic index (GI), has not been well examined. Aim: To investigate the effect of different starchy foods varying in their GI, on acute changes in dental plaque pH. Methods: In a series of sub-studies in healthy adults, common starchy carbohydrate foods, including white bread, instant mashed potatoes, canned chickpeas, pasta, breakfast cereals, white rice, and an oral glucose solution were consumed in fixed 25 g available carbohydrate portions. The change in dental plaque pH was assessed postprandially over 1 h and capillary plasma glucose was measured at regular intervals over 2 h. Results: Higher GI starchy foods produced greater acute plaque pH decreases and larger overall postprandial glucose responses compared to lower GI starchy foods (white bread compared with canned chickpeas: −1.5 vs. −0.7 pH units, p = 0.001, and 99 ± 8 mmol/L min vs. 47 ± 7 mmol/L min, p = 0.026). Controlling for other food factors (food form and nutritional composition), lower GI versions of matched food pairs produced smaller plaque pH excursions compared to higher GI versions of the same food. Using linear regression analysis, the GI value of starchy carbohydrate foods explained 60% of the variation in maximum plaque pH nadir and 64% of the variation in overall acute dental plaque pH excursion (p < 0.01). Conclusion: The findings imply that starchy foods, in particular those with a higher GI, may play a role in increasing the risk of dental caries.
Published:
2021-08
Title:
Unintended Consequences: Nutritional Impact and Potential Pitfalls of Switching from Animal- to Plant-Based Foods
Authors:
Tso, Rachel; Forde, Ciarán G.
Abstract:
Consumers are shifting towards plant-based diets, driven by both environmental and health reasons. This has led to the development of new plant-based meat alternatives (PBMAs) that are marketed as being sustainable and good for health. However, it remains unclear whether these novel PBMAs to replace animal foods carry the same established nutritional benefits as traditional plant-based diets based on pulses, legumes and vegetables. We modelled a reference omnivore diet using NHANES 2017–2018 data and compared it to diets that substituted animal products in the reference diet with either traditional or novel plant-based foods to create flexitarian, vegetarian and vegan diets matched for calories and macronutrients. With the exception of the traditional vegan diet, all diets with traditional plant-based substitutes met daily requirements for calcium, potassium, magnesium, phosphorus, zinc, iron and Vitamin B12 and were lower in saturated fat, sodium and sugar than the reference diet. Diets based on novel plant-based substitutes were below daily requirements for calcium, potassium, magnesium, zinc and Vitamin B12 and exceeded the reference diet for saturated fat, sodium and sugar. Much of the recent focus has been on protein quality and quantity, but our case study highlights the risk of unintentionally increasing undesirable nutrients while reducing the overall nutrient density of the diet when less healthy plant-based substitutes are selected. Opportunities exist for PBMA producers to enhance the nutrient profile and diversify the format of future plant-based foods that are marketed as healthy, sustainable alternatives to animal-based products.
Published:
2021-08
Title:
Cardiovascular disease in diabetes, beyond glucose
Authors:
Eckel, Robert H.; Bornfeldt, Karin E.; Goldberg, Ira J.
Abstract:
Despite the decades-old knowledge that diabetes mellitus is a major risk factor for cardiovascular disease, the reasons for this association are only partially understood. While this association is true for both type 1 and type 2 diabetes, different pathophysiological processes may be responsible. Lipids and other risk factors are indeed important, whereas the role of glucose is less clear. This lack of clarity stems from clinical trials that do not unambiguously show that intensive glycemic control reduces cardiovascular events. Animal models have provided mechanisms that link diabetes to increased atherosclerosis, and evidence consistent with the importance of factors beyond hyperglycemia has emerged. We review clinical, pathological, and animal studies exploring the pathogenesis of atherosclerosis in humans living with diabetes and in mouse models of diabetes. An increased effort to identify risk factors beyond glucose is now needed to prevent the increased cardiovascular disease risk associated with diabetes.
Published:
2021-07
Title:
Exogenous ketosis in patients with type 2 diabetes: Safety, tolerability and effect on glycaemic control
Authors:
Soto‐Mota, Adrian; Norwitz, Nicholas G.; Evans, Rhys; Clarke, Kieran; Barber, Thomas M.
Abstract:
Ketogenic diets have shown to improve glycaemic control in patients with type 2 diabetes. This study investigated the safety, tolerability, and effects on glycaemic control in patients with type 2 diabetes of an exogenous ketone monoester (KE) capable ...
Published:
2021-07
Title:
Ketogenic Diet Decreases Alcohol Intake in Adult Male Mice
Authors:
Blanco-Gandía, María del Carmen; Ródenas-González, Francisco; Pascual, María; Reguilón, Marina Daiana; Guerri, Consuelo; Miñarro, José; Rodríguez-Arias, Marta
Abstract:
The classic ketogenic diet is a diet high in fat, low in carbohydrates, and well-adjusted proteins. The reduction in glucose levels induces changes in the body’s metabolism, since the main energy source happens to be ketone bodies. Recent studies have suggested that nutritional interventions may modulate drug addiction. The present work aimed to study the potential effects of a classic ketogenic diet in modulating alcohol consumption and its rewarding effects. Two groups of adult male mice were employed in this study, one exposed to a standard diet (SD, n = 15) and the other to a ketogenic diet (KD, n = 16). When a ketotic state was stable for 7 days, animals were exposed to the oral self-administration paradigm to evaluate the reinforcing and motivating effects of ethanol. Rt-PCR analyses were performed evaluating dopamine, adenosine, CB1, and Oprm gene expression. Our results showed that animals in a ketotic state displayed an overall decrease in ethanol consumption without changes in their motivation to drink. Gene expression analyses point to several alterations in the dopamine, adenosine, and cannabinoid systems. Our results suggest that nutritional interventions may be a useful complementary tool in treating alcohol-use disorders.
Published:
2021-07
Title:
Meat and Human Health—Current Knowledge and Research Gaps
Authors:
Geiker, Nina Rica Wium; Bertram, Hanne C.; Mejborn, Heddie; Dragsted, Lars O.; Kristensen, Lars; Carrascal, Jorge R.; Bügel, Susanne; Astrup, Arne
Abstract:
Meat is highly nutritious and contributes with several essential nutrients which are difficult to obtain in the right amounts from other food sources. Industrially processed meat contains preservatives including salts, possibly exerting negative effects on health. During maturation, some processed meat products develop a specific microbiota, forming probiotic metabolites with physiological and biological effects yet unidentified, while the concentration of nutrients also increases. Meat is a source of saturated fatty acids, and current WHO nutrition recommendations advise limiting saturated fat to less than ten percent of total energy consumption. Recent meta-analyses of both observational and randomized controlled trials do not support any effect of saturated fat on cardiovascular disease or diabetes. The current evidence regarding the effect of meat consumption on health is potentially confounded, and there is a need for sufficiently powered high-quality trials assessing the health effects of meat consumption. Future studies should include biomarkers of meat intake, identify metabolic pathways and include detailed study of fermented and other processed meats and their potential of increasing nutrient availability and metabolic effects of compounds.
Published:
2021-07
Title:
Metabolic Phenotypes and Step by Step Evolution of Type 2 Diabetes: A New Paradigm
Authors:
Cooper, Isabella D.; Brookler, Kenneth H.; Kyriakidou, Yvoni; Elliott, Bradley T.; Crofts, Catherine A. P.
Abstract:
Unlike bolus insulin secretion mechanisms, basal insulin secretion is poorly understood. It is essential to elucidate these mechanisms in non-hyperinsulinaemia healthy persons. This establishes a baseline for investigation into pathologies where these processes are dysregulated, such as in type 2 diabetes (T2DM), cardiovascular disease (CVD), certain cancers and dementias. Chronic hyperinsulinaemia enforces glucose fueling, depleting the NAD+ dependent antioxidant activity that increases mitochondrial reactive oxygen species (mtROS). Consequently, beta-cell mitochondria increase uncoupling protein expression, which decreases the mitochondrial ATP surge generation capacity, impairing bolus mediated insulin exocytosis. Excessive ROS increases the Drp1:Mfn2 ratio, increasing mitochondrial fission, which increases mtROS; endoplasmic reticulum-stress and impaired calcium homeostasis ensues. Healthy individuals in habitual ketosis have significantly lower glucagon and insulin levels than T2DM individuals. As beta-hydroxybutyrate rises, hepatic gluconeogenesis and glycogenolysis supply extra-hepatic glucose needs, and osteocalcin synthesis/release increases. We propose insulin’s primary role is regulating beta-hydroxybutyrate synthesis, while the role of bone regulates glucose uptake sensitivity via osteocalcin. Osteocalcin regulates the alpha-cell glucagon secretory profile via glucagon-like peptide-1 and serotonin, and beta-hydroxybutyrate synthesis via regulating basal insulin levels. Establishing metabolic phenotypes aids in resolving basal insulin secretion regulation, enabling elucidation of the pathological changes that occur and progress into chronic diseases associated with ageing.
Published:
2021-07
Title:
Multisite Examination of Depression Screening Scores and Correlates Among Adolescents and Young Adults With Type 2 Diabetes
Authors:
Monaghan, Maureen; Mara, Constance A.; Kichler, Jessica C.; Westen, Sarah C.; Rawlinson, Alana; Jacobsen, Laura M.; Adams, Rebecca N.; Stone, Jenine Y.; Hood, Korey K.; Mulvaney, Shelagh A.
Abstract:
OBJECTIVES: Our aim was to evaluate self-reported depressive symptoms and clinical outcomes during routine screening for adolescents and young adults with type 2 diabetes (T2D), and examine associations among depressive symptoms and demographic and clinical characteristics. METHODS: The Patient Health Questionnaire (PHQ) was administered to 197 adolescents and young adults with T2D using the PHQ-2 or PHQ-9 in routine pediatric diabetes care at 4 academic medical centres. Data from electronic health records were extracted from the screening date and 12 months earlier. RESULTS: Adolescents and young adults with T2D (mean age, 16.85 years; 57% male; 77.2% non-Caucasian) completed the PHQ as part of routine diabetes care. On the PHQ, 19.3% of adolescents and young adults endorsed elevated depressive symptoms (PHQ score ≥10) and, among a subsample with item-level data (n=53), 18.9% endorsed thoughts of self-harm. Subsequently, 50.0% of those with depressive symptoms had a documented referral for mental health treatment in the electronic health record after the positive screening outcome. Older age, shorter diabetes duration, higher glycated hemoglobin level, being non-Hispanic white, more blood glucose checks per day and being prescribed oral medications were significantly associated with more depressive symptoms. CONCLUSIONS: Screening for depressive symptoms identifies individuals in need of referral for mental health treatment. A focus on self-harm assessment, standardized methods for documentation of symptoms and mental health referrals and increased referral resources are needed.
Published:
2021-07
Title:
Understanding the evolution of nutritive taste in animals: Insights from biological stoichiometry and nutritional geometry
Authors:
Demi, Lee M.; Taylor, Brad W.; Reading, Benjamin J.; Tordoff, Michael G.; Dunn, Robert R.
Abstract:
A major conceptual gap in taste biology is the lack of a general framework for understanding the evolution of different taste modalities among animal species. We turn to two complementary nutritional frameworks, biological stoichiometry theory and nutritional ...
Published:
2021-07
Title:
We and herbivores eat endophytes
Authors:
Martínez‐Romero, Esperanza; Aguirre‐Noyola, José Luis; Bustamante‐Brito, Rafael; González‐Román, Pilar; Hernández‐Oaxaca, Diana; Higareda‐Alvear, Víctor; Montes‐Carreto, Leslie M.; Martínez‐Romero, Julio César; Rosenblueth, Mónica; Servín‐Garcidueñas, Luis Eduardo
Abstract:
Here a cycle of endophytic‐enteric‐soil‐endophytic microbes is proposed which has relevance for health and comprises the fate of animal faeces as natural microbial inoculants for plants that constitute bacterial sources for animal ...
Published:
2021-07
Title:
β-Hydroxybutyrate, a Ketone Body, Potentiates the Antioxidant Defense via Thioredoxin 1 Upregulation in Cardiomyocytes
Authors:
Oka, Shin-ichi; Tang, Fan; Chin, Adave; Ralda, Guersom; Xu, Xiaoyong; Hu, Chengchen; Yang, Zhi; Abdellatif, Maha; Sadoshima, Junichi
Abstract:
Thioredoxin 1 (Trx1) is a major antioxidant that acts adaptively to protect the heart during the development of diabetic cardiomyopathy. The molecular mechanism(s) responsible for regulating the Trx1 level and/or activity during diabetic cardiomyopathy is unknown. β-hydroxybutyrate (βHB), a major ketone body in mammals, acts as an alternative energy source in cardiomyocytes under stress, but it also appears to be involved in additional mechanisms that protect the heart against stress. βHB upregulated Trx1 in primary cultured cardiomyocytes in a dose- and a time-dependent manner and a ketogenic diet upregulated Trx1 in the heart. βHB protected cardiomyocytes against H2O2-induced death, an effect that was abolished in the presence of Trx1 knockdown. βHB also alleviated the H2O2-induced inhibition of mTOR and AMPK, known targets of Trx1, in a Trx1-dependent manner, suggesting that βHB potentiates Trx1 function. It has been shown that βHB is a natural inhibitor of HDAC1 and knockdown of HDAC1 upregulated Trx1 in cardiomyocytes, suggesting that βHB may upregulate Trx1 through HDAC inhibition. βHB induced Trx1 acetylation and inhibited Trx1 degradation, suggesting that βHB-induced inhibition of HDAC1 may stabilize Trx1 through protein acetylation. These results suggest that βHB potentiates the antioxidant defense in cardiomyocytes through the inhibition of HDAC1 and the increased acetylation and consequent stabilization of Trx1. Thus, modest upregulation of ketone bodies in diabetic hearts may protect the heart through the upregulation of Trx1.
Published:
2021-07
Title:
Abdominal fat distribution modulates the metabolic effects of exogenous ketones in individuals with new-onset prediabetes after acute pancreatitis: Results from a randomized placebo-controlled trial
Authors:
Bharmal, Sakina H.; Alarcon Ramos, Gisselle C.; Ko, Juyeon; Petrov, Maxim S.
Abstract:
BACKGROUND AND AIMS: Exogenous ketone supplementation is emerging as a nutritional intervention that beneficially affects blood glucose control. We hypothesized that varying abdominal fat phenotypes play a role in the effect of exogenously induced ketosis. The aim was to investigate whether intra-abdominal fat distribution modulates the effect of exogenous ketones on glucoregulatory peptides in new-onset prediabetes. METHODS: Eighteen individuals with new-onset prediabetes after acute pancreatitis were randomized to receive a ketone monoester supplement or placebo in a crossover fashion. All participants underwent magnetic resonance imaging on a 3T scanner to determine their abdominal fat phenotypes. They were non-exclusively categorized as low adiposity or high adiposity phenotypes based on their abdominal and ectopic fat distribution (regardless of body mass index and waist circumference). Blood samples were analyzed for glucoregulatory peptides. Total area under the curve (AUC) over 150 min was calculated for each analyte. RESULTS: The total AUCs for insulin and C-peptide were significantly higher after ketone supplementation in individuals with high intra-pancreatic fat deposition, skeletal muscle fat deposition, and subcutaneous fat volume; and low visceral fat volume and intra-hepatic fat deposition. The total AUC for glucose-dependent insulinotropic peptide was significantly higher after ketone supplementation in individuals with high intra-pancreatic fat deposition, skeletal muscle fat deposition, subcutaneous fat volume, and visceral fat volume. The total AUC for glucagon-like peptide-1 was not associated with any adiposity phenotype. CONCLUSIONS: Individuals with high depositions of intra-pancreatic fat, skeletal muscle fat, subcutaneous fat may not achieve favorable outcomes of blood glucose control following ketone supplementation. Abdominal fat distribution is an important factor in the pathogenesis of new-onset prediabetes and it may influence the effectiveness of nutritional strategies designed for these individuals. REGISTERED UNDER CLINICALTRIALS. GOV IDENTIFIER NO: NCT03889210.
Published:
2021-06
Title:
Carbohydrate Restriction with or without Exercise Training Improves Blood Pressure and Insulin Sensitivity in Overweight Women
Authors:
Sun, Shengyan; Kong, Zhaowei; Shi, Qingde; Zhang, Haifeng; Lei, On-Kei; Nie, Jinlei
Abstract:
Objective: The purpose of this study was to evaluate the effects of a 4-week low-carbohydrate diet (LC) with or without exercise training on cardiometabolic health-related profiles in overweight/obese women. Methods: Fifty overweight/obese Chinese women (age: 22.2 ± 3.3 years, body mass index (BMI): 25.1 ± 3.1 kg·m−2) were randomized to either a LC control group (LC-CON, n = 16), a LC and high-intensity interval training group (LC-HIIT, n = 17), or a LC and moderate-intensity continuous training group (LC-MICT, n = 17). All groups consumed LC for 4 weeks, while the LC-HIIT and LC-MICT groups followed an additional five sessions of HIIT (10 × 6 s cycling sprints and 9 s rest intervals, 2.5 min in total) or MICT (cycling continuously at 50–60% of peak oxygen uptake (VO2peak) for 30 min) weekly. Blood pressure, fasting glucose, insulin sensitivity, and several metabolic or appetite regulating hormones were measured before and after intervention. Results: Significant reductions in body weight (− ~2.5 kg, p < 0.001, η2 = 0.772) and BMI (− ~1 unit, p < 0.001, η2 = 0.782) were found in all groups. Systolic blood pressure was reduced by 5–6 mmHg (p < 0.001, η2 = 0.370); fasting insulin, leptin, and ghrelin levels were also significantly decreased (p < 0.05), while insulin sensitivity was improved. However, there were no significant changes in fasting glucose, glucagon, and gastric inhibitory peptide levels. Furthermore, no group differences were found among the three groups, suggesting that extra training (i.e., LC-HIIT and LC-MICT) failed to trigger additional effects on these cardiometabolic profiles. Conclusions: The short-term carbohydrate restriction diet caused significant weight loss and improved blood pressure and insulin sensitivity in the overweight/obese women, although the combination with exercise training had no additional benefits on the examined cardiometabolic profiles. Moreover, the long-term safety and effectiveness of LC needs further study.
Published:
2021-06
Title:
Depression and Vegetarians: Association between Dietary Vitamin B6, B12 and Folate Intake and Global and Subcortical Brain Volumes
Authors:
Berkins, Samuel; Schiöth, Helgi Birgir; Rukh, Gull
Abstract:
Deficiency of vitamin B6 and vitamin B12, mostly in vegetarians, is found to be associated with depression and adverse neurological function. We investigated whether vitamin B6, B12, and folate have an effect on brain structure, especially among depressed people who follow a specific diet. The study sample comprised 9426 participants from the UK Biobank cohort with a mean age of 62.4 years. A generalized linear model controlling for age, sex, body mass index, ethnicity, town send deprivation index, educational qualification, smoking, and alcohol intake was used to test the association between study groups and structural brain volumes. Depression was more prevalent, and intake of vitamin B6 and B12 was lower among vegetarians, while non-vegetarians had a lower intake of folate. Overall, no significant association was observed between vitamin B6, B12, and folate intakes and both global and subcortical brain volumes among participants with depression. However, vitamin B12 intake was positively associated with right pallidum among non-depressed participants, and a significant interaction between vitamin B12 intake and depression status on the right pallidum was observed. Also, a significant interaction between folate intake and depression status on grey matter (GM) volume and left thalamus was observed. Upon diet stratification, folate intake is associated with total brain volume and GM volume among vegetarians with depression. Furthermore, no significant associations were observed for subcortical regions. Our findings suggest that dietary intake of vitamin B6 and B12 might have an effect on brain structure. Vegetarians, particularly those who suffer from depression may benefit from supplementing their diets with vitamins B6, B12, and folate to ensure brain health. Further studies, especially with a larger sample size and longitudinal design, are needed to confirm these findings.
Published:
2021-06
Title:
Dietary Intake of n-3 PUFA-Enriched Hen Eggs Changes Inflammatory Markers’ Concentration and Treg/Th17 Cells Distribution in Blood of Young Healthy Adults—A Randomised Study
Authors:
Kolobarić, Nikolina; Drenjančević, Ines; Matić, Anita; Šušnjara, Petar; Mihaljević, Zrinka; Mihalj, Martina
Abstract:
In the present study, we aimed to determine the effects of n-3 polyunsaturated acid (PUFA) supplementation (~1053 mg/per day), i.e., α-linolenic (~230 mg), eicosapentaenoic (~15 mg), and docosahexaenoic acid (~105 mg), through hen eggs, on pro- and anti-inflammatory parameters in healthy individuals (23.8 ± 2.57 years old). Here, we demonstrate differential effects of regular hen eggs (N = 21; W/M = 10/11) and n-3 PUFA-enriched hen eggs (N = 19; W/M = 10/9) consumption on the serum levels of lipid mediators, representation of peripheral T helper cell subsets (recently activated T-helper cells, nTreg, Th17 and non-Th17-IL-17A secreting T-helper lymphocytes) and their functional capacity for cytokine secretion. Both diets significantly altered systemic levels of pro-inflammatory and inflammation resolving lipid mediators; however, only the n-3 PUFAs group showed a significant shift towards anti-inflammatory prostanoids and increased levels of pro-resolving oxylipins. Both study groups showed reduced frequencies of peripheral nTreg lymphocytes and decreased rates of peripheral Th17 cells. Their functional capacity for cytokine secretion was significantly altered only in the n-3 PUFAs group in terms of increased transforming growth factor β-1 and reduced interleukin 6 secretion. Diet supplemented with n-3 PUFAs alters immune response towards inflammation resolving conditions through effects on lipid mediators and cytokine secretion by T lymphocytes in human model without underlying comorbidities.
Published:
2021-06
Title:
Divergence-time estimates for hominins provide insight into encephalization and body mass trends in human evolution
Authors:
Püschel, Hans P.; Bertrand, Ornella C.; O’Reilly, Joseph E.; Bobe, René; Püschel, Thomas A.
Abstract:
Quantifying speciation times during human evolution is fundamental as it provides a timescale to test for the correlation between key evolutionary transitions and extrinsic factors such as climatic or environmental change. Here, we applied a total evidence dating approach to a hominin phylogeny to estimate divergence times under different topological hypotheses. The time-scaled phylogenies were subsequently used to perform ancestral state reconstructions of body mass and phylogenetic encephalization quotient (PEQ). Our divergence-time estimates are consistent with other recent studies that analysed extant species. We show that the origin of the genus Homo probably occurred between 4.30 and 2.56 million years ago. The ancestral state reconstructions show a general trend towards a smaller body mass before the emergence of Homo, followed by a trend towards a greater body mass. PEQ estimations display a general trend of gradual but accelerating encephalization evolution. The obtained results provide a rigorous temporal framework for human evolution.
Published:
2021-06
Title:
Elevated dietary ω-6 polyunsaturated fatty acids induce reversible peripheral nerve dysfunction that exacerbates comorbid pain conditions
Authors:
Boyd, Jacob T.; LoCoco, Peter M.; Furr, Ashley R.; Bendele, Michelle R.; Tram, Meilinn; Li, Qun; Chang, Fang-Mei; Colley, Madeline E.; Samenuk, Grace M.; Arris, Dominic A.; Locke, Erin E.; Bach, Stephan B. H.; Tobon, Alejandro; Ruparel, Shivani B.; Hargreaves, Kenneth M.
Abstract:
Chronic pain is the leading cause of disability worldwide1 and is commonly associated with comorbid disorders2. However, the role of diet in chronic pain is poorly understood. Of particular interest is the Western-style diet, enriched with ω-6 polyunsaturated fatty acids (PUFAs) that accumulate in membrane phospholipids and oxidise into pronociceptive oxylipins3,4. Here we report that mice administered an ω-6 PUFA-enriched diet develop persistent nociceptive hypersensitivities, spontaneously active and hyper-responsive glabrous afferent fibres and histologic markers of peripheral nerve damage reminiscent of a peripheral neuropathy. Linoleic and arachidonic acids accumulate in lumbar dorsal root ganglia, with increased liberation via elevated phospholipase (PLA)2 activity. Pharmacological and molecular inhibition of PLA2G7 or diet reversal with high levels of ω-3 PUFAs attenuate nociceptive behaviours, neurophysiologic abnormalities and afferent histopathology induced by high ω-6 intake. Additionally, ω-6 PUFA accumulation exacerbates allodynia observed in preclinical inflammatory and neuropathic pain models and is strongly correlated with multiple pain indices of clinical diabetic neuropathy. Collectively, these data reveal dietary enrichment with ω-6 PUFAs as a new aetiology of peripheral neuropathy and risk factor for chronic pain and implicate multiple therapeutic considerations for clinical pain management.
Published:
2021-06
Title:
Gut flora and metabolism are altered in epilepsy and partially restored after ketogenic diets
Authors:
Gong, Xue; Cai, Qianyun; Liu, Xu; An, Dongmei; Zhou, Dong; Luo, Rong; Peng, Rong; Hong, Zhen
Abstract:
OBJECTIVE: The aim of this study was to investigate the composition of the intestinal microbiota and its association with fecal short chain fatty acids (SCFAs) in children with drug refractory epilepsy (DRE) before and after treatment with a ketogenic diet (KD). METHODS: Herein, we conducted a cross-sectional study of 12 children with DRE and 12 matched healthy controls to compare the changes in fecal microbiomes and SCFAs. Disease cohort also underwent analysis before and after 6 months of KD treatment. RESULTS: A higher microbial alpha diversity and a significant increase in Actinobacteria at the phylum level and Enterococcus, Anaerostipes, Bifidobacterium, Bacteroides, and Blautia at the genus level were observed in the children with DRE. The abundance of the eight epileptic-associated genera was reversed after six months of KD treatment with decreases in Bifidobacterium, Akkermansia, Enterococcaceae and Actinomyces and increases in Subdoligranulum, Dialister, Alloprevotella (p
Published:
2021-06
Title:
Incidence and Characteristics of Kidney Stones in Patients on Ketogenic Diet: A Systematic Review and Meta-Analysis
Authors:
Acharya, Prakrati; Acharya, Chirag; Thongprayoon, Charat; Hansrivijit, Panupong; Kanduri, Swetha R.; Kovvuru, Karthik; Medaura, Juan; Vaitla, Pradeep; Garcia Anton, Desiree F.; Mekraksakit, Poemlarp; Pattharanitima, Pattharawin; Bathini, Tarun; Cheungpasitporn, Wisit
Abstract:
Very-low-carbohydrate diets or ketogenic diets are frequently used for weight loss in adults and as a therapy for epilepsy in children. The incidence and characteristics of kidney stones in patients on ketogenic diets are not well studied. Methods: A systematic literature search was performed, using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from the databases’ inception through April 2020. Observational studies or clinical trials that provide data on the incidence and/or types of kidney stones in patients on ketogenic diets were included. We applied a random-effects model to estimate the incidence of kidney stones. Results: A total of 36 studies with 2795 patients on ketogenic diets were enrolled. The estimated pooled incidence of kidney stones was 5.9% (95% CI, 4.6–7.6%, I2 = 47%) in patients on ketogenic diets at a mean follow-up time of 3.7 +/− 2.9 years. Subgroup analyses demonstrated the estimated pooled incidence of kidney stones of 5.8% (95% CI, 4.4–7.5%, I2 = 49%) in children and 7.9% (95% CI, 2.8–20.1%, I2 = 29%) in adults, respectively. Within reported studies, 48.7% (95% CI, 33.2–64.6%) of kidney stones were uric stones, 36.5% (95% CI, 10.6–73.6%) were calcium-based (CaOx/CaP) stones, and 27.8% (95% CI, 12.1–51.9%) were mixed uric acid and calcium-based stones, respectively. Conclusions: The estimated incidence of kidney stones in patients on ketogenic diets is 5.9%. Its incidence is approximately 5.8% in children and 7.9% in adults. Uric acid stones are the most prevalent kidney stones in patients on ketogenic diets followed by calcium-based stones. These findings may impact the prevention and clinical management of kidney stones in patients on ketogenic diets.
Published:
2021-06
Title:
Omega-3 Fatty Acids and Their Role in Pediatric Cancer
Authors:
Podpeskar, Alexandra; Crazzolara, Roman; Kropshofer, Gabriele; Hetzer, Benjamin; Meister, Bernhard; Müller, Thomas; Salvador, Christina
Abstract:
Background: Malnutrition is common in children with cancer and is associated with adverse clinical outcomes. The need for supportive care is becoming ever more evident and the role of nutrition in oncology is still not sufficiently understood. In particular, the consequences of macro- and micronutrient deficiencies require further research. As epidemiological data suggest anti-tumoral properties of omega-3 (n-3) polyunsaturated fatty acids (PUFAs), we reviewed the role of nutrition and n-3 supplementation in pediatric oncology. Methods: A comprehensive literature search was conducted on PubMed through 5 February 2021 to select meta-analyses, systematic reviews, observational studies, and individual randomized controlled trials (RCTs) on macro- and micronutrient supplementation in pediatric oncology. The search strategy included the following medical subject headings (MeSH) and keywords: “childhood cancer”, “pediatric oncology”, “nutritional status”, “malnutrition”, and “omega-3-fatty-acids”. The reference lists of all relevant articles were screened to include potentially pertinent studies. Results: We summarize evidence about the importance of adequate nutrition in childhood cancer and the role of n-3 PUFAs and critically interpret findings. Possible effects of supplementation on the nutritional status and benefits during chemotherapy are discussed as well as strategies for primary and secondary prevention. Conclusion: We here describe the obvious benefits of omega-3 supplementation in childhood cancer. Further large scale clinical trials are required to verify potential anti-cancer effects of n-3 fatty acids.
Published:
2021-06
Title:
The perioperative transition of serum biomarkers of a 1.5-year-old boy with very-long-chain acyl-CoA dehydrogenase deficiency
Authors:
Bo, Ryosuke; Awano, Hiroyuki; Yamada, Kenji; Ooi, Mayu; Okata, Yuichi; Bitoh, Yuko; Mizobuchi, Satoshi; Iijima, Kazumoto
Abstract:
Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD, OMIM 201475) is a congenital fatty acid oxidation disorder. Individuals with VLCADD should avoid catabolic states, including strenuous exercise and long-term fasting; however, such conditions are required when undergoing surgery. The perioperative management of VLCADD in infants has rarely been reported and details regarding the transition of serum biomarkers reflecting catabolic status have not been disclosed. Herein, we present the perioperative clinical and biological data of cryptorchidism in a 1.5-year-old boy with VLCADD. The patient was diagnosed through newborn screening and his clinical course was very stable. Genetic testing of ACADVL revealed compound heterozygous variants c.506 T > C (p.Met169Thr) and c.606-609delC (p.L216*). The enzyme activity of the patient with VLCAD was only 20% compared to that of healthy control. Left orchiopexy for the pediatric cryptorchidism was planned and performed at 1 and a half year of age. Induction anesthesia involved thiopental, fentanyl and rocuronium. The glucose infusion rate was maintained above 6.6 mg/kg/min starting the day before surgery until the operation was completed. Anesthesia was maintained with sevoflurane at approximately 2%. The serum concentration of tetradecenoylcarnitine were stable during the operation, ranging between 0.08 and 0.19 μM (cutoff
Published:
2021-06
Title:
Treatment of NAFLD with intermittent calorie restriction or low-carb high-fat diet - a randomised controlled trial
Authors:
Holmer, Magnus; Lindqvist, Catarina; Petersson, Sven; Moshtaghi-Svensson, John; Tillander, Veronika; Brismar, Torkel B.; Hagström, Hannes; Stål, Per
Abstract:
Background & Aims: The first-line treatment for non-alcoholic fatty liver disease (NAFLD) is weight reduction. Several diets have been proposed, with various effects specifically on liver steatosis. This trial compared the effects of intermittent calorie restriction (the 5:2 diet) and a low-carb high-fat diet (LCHF) on reduction of hepatic steatosis. Methods: We conducted an open-label randomised controlled trial that included 74 patients with NAFLD randomised in a 1:1:1 ratio to 12 weeks' treatment with either a LCHF or 5:2 diet, or general lifestyle advice from a hepatologist (standard of care; SoC). The primary outcome was reduction of hepatic steatosis as measured by magnetic resonance spectroscopy. Secondary outcomes included transient elastography, insulin resistance, blood lipids, and anthropometrics. Results: The LCHF and 5:2 diets were both superior to SoC treatment in reducing steatosis (absolute reduction: LCHF: -7.2% [95% CI = -9.3 to -5.1], 5:2: -6.1% [95% CI = -8.1 to -4.2], SoC: -3.6% [95% CI = -5.8 to -1.5]) and body weight (LCHF: -7.3 kg [95% CI = -9.6 to -5.0]; 5:2: -7.4 kg [95% CI = -8.7 to -6.0]; SoC: -2.5 kg [95% CI =-3.5 to -1.5]. There was no difference between 5:2 and LCHF (p = 0.41 for steatosis and 0.78 for weight). Liver stiffness improved in the 5:2 and SoC but not in the LCHF group. The 5:2 diet was associated with reduced LDL levels and was tolerated to a higher degree than LCHF. Conclusions: The LCHF and 5:2 diets were more effective in reducing steatosis and body weight in patients with NAFLD than SoC, suggesting dietary advice can be tailored to meet individual preferences. Lay summary: For a person with obesity who suffers from fatty liver, weight loss through diet can be an effective treatment to improve the condition of the liver. Many popular diets that are recommended for weight reduction, such as high-fat diets and diets based on intermittent fasting, have not had their effects on the liver directly evaluated. This study shows that both a low-carb high-fat and the 5:2 diet are effective in treating fatty liver caused by obesity. Clinical Trials Registration: This study is registered at Clinicaltrials.gov (NCT03118310).
Published:
2021-06
Title:
Weight change and glycemic control in type 2 diabetes patients during COVID-19 pandemic: the lockdown effect
Authors:
Biamonte, Emilia; Pegoraro, Francesco; Carrone, Flaminia; Facchi, Isabella; Favacchio, Giuseppe; Lania, Andrea Gerardo; Mazziotti, Gherardo; Mirani, Marco
Abstract:
PURPOSE: The aim of this study was to evaluate the impact of the COVID-19 lockdown occurred in Italy from March 9th to May 18th, 2020 on anthropometric parameters and glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: One hundred twenty-eight consecutive patients with T2DM (median age 70 years, 74 males) were retrospectively evaluated at the end of the lockdown period. Data on metabolic control were collected at different time: within three months before the lockdown (visit 0) and within the first six weeks after it (visit 1). RESULTS: During the lockdown, a significant increase in body weight (from 79.7 ± 18.7 kg to 81.4 ± 19.4 kg, p < 0.001), body mass index (BMI, from 29.5 ± 6 kg/m2 to 30.1 ± 6.3 kg/m2, p < 0.001), waist circumference (from 103.8 ± 13 cm to 105 ± 13.6 cm, p < 0.001), fasting plasma glucose (FPG; from 138.1 ± 29.4 mg/dL to 146.6 ± 36.4 mg/dL) and glycated hemoglobin (HbA1c; from 7 ± 0.8 to 7.3 ± 0.9%, p < 0.001) was observed. Weight gain was directly associated with HbA1c increase (β 0.085, C.I. 95% 0.05-0.121; p
Published:
2021-06
Title:
A review of biomarkers in the context of type 1 diabetes: Biological sensing for enhanced glucose control
Authors:
Wolkowicz, Kelilah L.; Aiello, Eleonora M.; Vargas, Eva; Teymourian, Hazhir; Tehrani, Farshad; Wang, Joseph; Pinsker, Jordan E.; Doyle, Francis J.; Patti, Mary-Elizabeth; Laffel, Lori M.; Dassau, Eyal
Abstract:
As wearable healthcare monitoring systems advance, there is immense potential for biological sensing to enhance the management of type 1 diabetes (T1D). The aim of this work is to describe the ongoing development of biomarker analytes in the context of T1D. Technological advances in transdermal biosensing offer remarkable opportunities to move from research laboratories to clinical point-of-care applications. In this review, a range of analytes, including glucose, insulin, glucagon, cortisol, lactate, epinephrine, and alcohol, as well as ketones such as beta-hydroxybutyrate, will be evaluated to determine the current status and research direction of those analytes specifically relevant to T1D management, using both in-vitro and on-body detection. Understanding state-of-the-art developments in biosensing technologies will aid in bridging the gap from bench-to-clinic T1D analyte measurement advancement.
Published:
2021-05
Title:
Animal Harms and Food Production: Informing Ethical Choices
Authors:
Hampton, Jordan O.; Hyndman, Timothy H.; Allen, Benjamin L.; Fischer, Bob
Abstract:
Consideration of animal welfare in food choices has become an influential contemporary theme. Traditional animal welfare views about food have been largely restricted to direct and intentional harms to livestock in intensive animal agriculture settings. ...
Published:
2021-05
Title:
Diabetes and Thrombosis: A Central Role for Vascular Oxidative Stress
Authors:
Vaidya, Aishwarya R.; Wolska, Nina; Vara, Dina; Mailer, Reiner K.; Schröder, Katrin; Pula, Giordano
Abstract:
Diabetes mellitus is the fifth most common cause of death worldwide. Due to its chronic nature, diabetes is a debilitating disease for the patient and a relevant cost for the national health system. Type 2 diabetes mellitus is the most common form of diabetes mellitus (90% of cases) and is characteristically multifactorial, with both genetic and environmental causes. Diabetes patients display a significant increase in the risk of developing cardiovascular disease compared to the rest of the population. This is associated with increased blood clotting, which results in circulatory complications and vascular damage. Platelets are circulating cells within the vascular system that contribute to hemostasis. Their increased tendency to activate and form thrombi has been observed in diabetes mellitus patients (i.e., platelet hyperactivity). The oxidative damage of platelets and the function of pro-oxidant enzymes such as the NADPH oxidases appear central to diabetes-dependent platelet hyperactivity. In addition to platelet hyperactivity, endothelial cell damage and alterations of the coagulation response also participate in the vascular damage associated with diabetes. Here, we present an updated interpretation of the molecular mechanisms underlying vascular damage in diabetes, including current therapeutic options for its control.
Published:
2021-05
Title:
Ketone Body 3-Hydroxybutyrate Ameliorates Atherosclerosis via Receptor Gpr109a-Mediated Calcium Influx
Authors:
Zhang, Shu-Jie; Li, Zi-Hua; Zhang, Yu-Dian; Chen, Jin; Li, Yuan; Wu, Fu-Qing; Wang, Wei; Cui, Zong Jie; Chen, Guo-Qiang
Abstract:
Atherosclerosis is a chronic inflammatory disease that can cause acute cardiovascular events. Activation of the NOD-like receptor family, pyrin domain containing protein 3 (NLRP3) inflammasome enhances atherogenesis, which links lipid metabolism to sterile inflammation. This study examines the impact of an endogenous metabolite, namely ketone body 3-hydroxybutyrate (3-HB), on a mouse model of atherosclerosis. It is found that daily oral administration of 3-HB can significantly ameliorate atherosclerosis. Mechanistically, 3-HB is found to reduce the M1 macrophage proportion and promote cholesterol efflux by acting on macrophages through its receptor G-protein-coupled receptor 109a (Gpr109a). 3-HB-Gpr109a signaling promotes extracellular calcium (Ca2+) influx. The elevation of intracellular Ca2+ level reduces the release of Ca2+ from the endothelium reticulum (ER) to mitochondria, thus inhibits ER stress triggered by ER Ca2+ store depletion. As NLRP3 inflammasome can be activated by ER stress, 3-HB can inhibit the activation of NLRP3 inflammasome, which triggers the increase of M1 macrophage proportion and the inhibition of cholesterol efflux. It is concluded that daily nutritional supplementation of 3-HB attenuates atherosclerosis in mice.
Published:
2021-05
Title:
The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic ß-cell function in overweight/obese men: a single-arm uncontrolled study
Authors:
La Vignera, Sandro; Cannarella, Rossella; Galvano, Fabio; Grillo, Agata; Aversa, Antonio; Cimino, Laura; Magagnini, Cristina M.; Mongioì, Laura M.; Condorelli, Rosita A.; Calogero, Aldo E.
Abstract:
Background Overweight and obesity are increasingly spread in our society. Low testosterone levels are often present in these patients, the so-called metabolic hypogonadism, that further alters the metabolic balance in a sort of vicious cycle. Very low-calorie ketogenic diet (VLCKD) has been reported to efficiently reduce body weight, glycaemia, and the serum levels of insulin, glycated hemoglobin, but its effects on β-cell function and total testosterone (TT) levels are less clear. Aim To evaluate the effects of VLCKD on markers suggested to be predictive of β-cell dysfunction development, such as proinsulin or proinsulin/insulin ratio, and on TT values in a cohort of overweight or obese nondiabetic male patients with metabolic hypogonadism. Methods Patients with overweight or obesity and metabolic hypogonadism underwent to VLCKD for 12 weeks. Anthropometric parameters, blood testing for the measurement of glycaemia, insulin, C-peptide, proinsulin, TT, calculation of body-mass index (BMI), and HOMA index were performed before VLCKD and after 12 weeks. Results Twenty patients (mean age 49.3 ± 5.2 years) were enrolled. At enrollement all patients presented increased insulin, HOMA index, C-peptide, and proinsulin levels, whereas the proinsulin/insulin ratio was within the normal values. After VLCKD treatment, body weight and BMI significantly decreased, and 14.9 ± 3.9% loss of the initial body weight was achieved. Glycaemia, insulin, HOMA index, C-peptide, and proinsulin significantly decreased compared to pre-VLCKD levels. Serum glycaemia, insulin, C-peptide, and proinsulin levels returned within the normal range in all patients. No difference in the proinsulin/insulin ratio was observed after VLCKD treatment. A mean increase of 218.1 ± 53.9% in serum TT levels was achieved and none of the patients showed TT values falling in the hypogonadal range at the end of the VLCKD treatment. Conclusions This is the first study that evaluated the effects of VLCKD on proinsulin, proinsulin/insulin ratio, and TT levels. VLCKD could be safely used to improve β-cell secretory function and insulin-sensitivity, and to rescue overweight and obese patients from β-cell failure and metabolic hypogonadism.
Published:
2021-05
Title:
The use of the ketogenic diet in the treatment of psychiatric disorders
Authors:
Tillery, Erika E.; Ellis, Katie D.; Threatt, Tiffaney B.; Reyes, Hannah A.; Plummer, Christopher S.; Barney, Logan R.
Abstract:
Introduction: The ketogenic diet (KD) is a high-fat, low-carbohydrate, and moderate-protein diet that has shown benefit as a treatment in neurologic disorders and may serve as a therapeutic option in individuals with psychiatric disorders. Methods: A search was conducted using EBSCOhost and PubMed databases for studies relating to ketogenic or low-carbohydrate diets and psychiatric disorders. Results: A total of 32 experimental or observational studies were identified by initial search strategies, 14 of which met the criteria to be included in this analysis. Although specific diet formulations varied somewhat between studies, they all generally examined low-carbohydrate dietary intake with the goal of producing a ketotic state. The studies included in this review indicated the KD was beneficial in reducing symptoms associated with various psychiatric disorders. Discussion: This review summarizes the available evidence regarding the efficacy of the ketogenic diet in psychiatric disease states. Data from the studies analyzed demonstrated a positive response in individuals who were able to remain on the diet, regardless of the disease state. However, there is a need for more data to clearly define the specific benefits the KD may provide.
Published:
2021-05
Title:
Time-Restricted Feeding and Metabolic Outcomes in a Cohort of Italian Adults
Authors:
Currenti, Walter; Buscemi, Silvio; Cincione, Raffaele Ivan; Cernigliaro, Achille; Godos, Justyna; Grosso, Giuseppe; Galvano, Fabio
Abstract:
Background: research exploring the effects of food timing and frequency on health and disease is currently ongoing. While there is an increasing body of scientific literature showing the potential health benefits of intermittent fasting (IF) in laboratory settings and in animals, studies regarding IF on humans are limited. Therefore, the objective of this research was to evaluate the relationship between the feeding/fasting time window and metabolic outcomes among adult individuals. Methods: dietary and demographic data of 1936 adult subjects living in the south of Italy were examined. Food frequency questionnaires (FFQ) were administered to determine the period of time between the first and the last meal of a typical day. Subjects were then divided into those with a time feeding window lasting more than 10 h, within 8 h (TRF-8) and within 10 h. Results: after adjustment for potential confounding factors related to eating habits (such as adherence to the Mediterranean diet, having breakfast/dinner), TRF-10 was inversely associated with being overweight/obese (OR = 0.05, 95% CI: 0.01, 0.07), hypertension (OR = 0.24, 95% CI: 0.13, 0.45), and dyslipidemias (OR = 0.26, 95% CI: 0.10, 0.63), while TRF-8 only with being overweight/obese (OR = 0.08, 95% CI: 0.04, 0.15) and hypertension (OR = 0.33, 95% CI: 0.17, 0.60). No associations were found with type-2 diabetes. Conclusions: individuals with a restricted feeding time window were less likely to be overweight, obese and hypertensive. Further studies are needed to clearly validate the results of the present study.
Published:
2021-05
Title:
Changes in Gut Microbiota after a Four-Week Intervention with Vegan vs. Meat-Rich Diets in Healthy Participants: A Randomized Controlled Trial
Authors:
Kohnert, Eva; Kreutz, Clemens; Binder, Nadine; Hannibal, Luciana; Gorkiewicz, Gregor; Müller, Alexander; Storz, Maximilian Andreas; Huber, Roman; Lederer, Ann-Kathrin
Abstract:
An essential role of the gut microbiota in health and disease is strongly suggested by recent research. The composition of the gut microbiota is modified by multiple internal and external factors, such as diet. A vegan diet is known to show beneficial health effects, yet the role of the gut microbiota is unclear. Within a 4-week, monocentric, randomized, controlled trial with a parallel group design (vegan (VD) vs. meat-rich (MD)) with 53 healthy, omnivore, normal-weight participants (62% female, mean 31 years of age), fecal samples were collected at the beginning and at the end of the trial and were analyzed using 16S rRNA gene amplicon sequencing (Clinical Trial register: DRKS00011963). Alpha diversity as well as beta diversity did not differ significantly between MD and VD. Plotting of baseline and end samples emphasized a highly intra-individual microbial composition. Overall, the gut microbiota was not remarkably altered between VD and MD after the trial. Coprococcus was found to be increased in VD while being decreased in MD. Roseburia and Faecalibacterium were increased in MD while being decreased in VD. Importantly, changes in genera Coprococcus, Roseburia and Faecalibacterium should be subjected to intense investigation as markers for physical and mental health.
Published:
2021-04
Title:
Effects of Calorie Restriction on Health Span and Insulin Resistance: Classic Calorie Restriction Diet vs. Ketosis-Inducing Diet
Authors:
Napoleão, Ana; Fernandes, Lívia; Miranda, Cátia; Marum, Ana Paula
Abstract:
As the incidence of Chronic Non-Communicable Diseases (CNCDs) increases, preventive approaches become more crucial. In this review, calorie restriction (CR) effects on human beings were evaluated, comparing the benefits and risks of different CR diets: classic CR vs. ketosis-inducing diets, including intermittent fasting (IF), classic ketogenic diet (CKD), fasting mimicking diet (FMD), very-low-calorie ketogenic Diet (VLCKD) and Spanish ketogenic Mediterranean diet (SKMD). Special emphasis on insulin resistance (IR) was placed, as it mediates metabolic syndrome (MS), a known risk factor for CNCD, and is predictive of MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.
Published:
2021-04
Title:
Histamine Intolerance Originates in the Gut
Authors:
Schnedl, Wolfgang J.; Enko, Dietmar
Abstract:
Histamine intolerance (HIT) is assumed to be due to a deficiency of the gastrointestinal (GI) enzyme diamine oxidase (DAO) and, therefore, the food component histamine not being degraded and/or absorbed properly within the GI tract. Involvement of the GI mucosa in various disorders and diseases, several with unknown origin, and the effects of some medications seem to reduce gastrointestinal DAO activity. HIT causes variable, functional, nonspecific, non-allergic GI and extra-intestinal complaints. Usually, evaluation for HIT is not included in differential diagnoses of patients with unexplained, functional GI complaints or in the here-listed disorders and diseases. The clinical diagnosis of HIT is challenging, and the thorough anamnesis of all HIT-linked complaints, using a standardized questionnaire, is the mainstay of HIT diagnosis. So far, DAO values in serum have not been established to correlate with DAO activity in the gut, but the diagnosis of HIT may be supported with determination of a low serum DAO value. A targeted dietary intervention, consisting of a histamine-reduced diet and/or supplementation with oral DAO capsules, is helpful to reduce HIT-related symptoms. This manuscript will present why histamine should also be taken into account in the differential diagnoses of patients with various diseases and disorders of unknown origin, but with association to functional gastrointestinal complaints. In this review, we discuss currently increasing evidence that HIT is primarily a gastrointestinal disorder and that it originates in the gut.
Published:
2021-04
Title:
Ketogenic Diet in Infants with Early-Onset Epileptic Encephalopathy and SCN2A Mutation
Authors:
Tian, Xiaoyu; Zhang, Yange; Zhang, Jinhong; Lu, Yan; Men, Xinyi; Wang, Xiuxia
Abstract:
Research has shown mutations in the voltage-gated sodium channel gene SCN2A to be associated with developmental delays and infantile seizures in patients with early-onset epileptic encephalopathies (EOEEs). Here, we report the case of an infant with a de novo SCN2A mutation with EOEE who had medically refractory seizures that improved with a ketogenic diet (KD) implemented at an age less than 2 months. On the day of his birth, the infant presented with a pattern of convulsions with dozens of episodes per day. An initial video electroencephalogram revealed poor reactivity of background activity, with multiple partial episodes starting from the right temporal region, and abnormal electrical activity in the right hemisphere. The seizures previously were not controlled with successive therapy with phenobarbital, topiramate, and levetiracetam. Genetic testing revealed the presence of a mutation in the SCN2A gene (c.4425C>G, p.Asn1475Lys). The infant's seizures decreased significantly with a combination of KD and medication. The present case exemplifies the potential for personalized genomics in identifying the etiology of an illness. Furthermore, the KD appears to feasible in infants younger than 2 months and might elicit good responses to EOEE associated with SCN2A mutation.
Published:
2021-04
Title:
Possible Neuroprotective Effects of l-Carnitine on White-Matter Microstructural Damage and Cognitive Decline in Hemodialysis Patients
Authors:
Ueno, Yuji; Saito, Asami; Nakata, Junichiro; Kamagata, Koji; Taniguchi, Daisuke; Motoi, Yumiko; Io, Hiroaki; Andica, Christina; Shindo, Atsuhiko; Shiina, Kenta; Miyamoto, Nobukazu; Yamashiro, Kazuo; Urabe, Takao; Suzuki, Yusuke; Aoki, Shigeki; Hattori, Nobutaka
Abstract:
Although l-carnitine alleviated white-matter lesions in an experimental study, the treatment effects of l-carnitine on white-matter microstructural damage and cognitive decline in hemodialysis patients are unknown. Using novel diffusion magnetic resonance imaging (dMRI) techniques, white-matter microstructural changes together with cognitive decline in hemodialysis patients and the effects of l-carnitine on such disorders were investigated. Fourteen hemodialysis patients underwent dMRI and laboratory and neuropsychological tests, which were compared across seven patients each in two groups according to duration of l-carnitine treatment: (1) no or short-term l-carnitine treatment (NSTLC), and (2) long-term l-carnitine treatment (LTLC). Ten age- and sex-matched controls were enrolled. Compared to controls, microstructural disorders of white matter were widely detected on dMRI of patients. An autopsy study of one patient in the NSTLC group showed rarefaction of myelinated fibers in white matter. With LTLC, microstructural damage on dMRI was alleviated along with lower levels of high-sensitivity C-reactive protein and substantial increases in carnitine levels. The LTLC group showed better achievement on trail making test A, which was correlated with amelioration of disorders in some white-matter tracts. Novel dMRI tractography detected abnormalities of white-matter tracts after hemodialysis. Long-term treatment with l-carnitine might alleviate white-matter microstructural damage and cognitive impairment in hemodialysis patients.
Published:
2021-04
Title:
Soft drinks and sweeteners intake: Possible contribution to the development of metabolic syndrome and cardiovascular diseases. Beneficial or detrimental action of alternative sweeteners?
Authors:
Schiano, Concetta; Grimaldi, Vincenzo; Scognamiglio, Michele; Costa, Dario; Soricelli, Andrea; Nicoletti, Giovanni Francesco; Napoli, Claudio
Abstract:
The rapid increase in obesity, metabolic syndrome, and cardiovascular diseases (CVDs) has been related to the rise in sugar-added foods and sweetened beverages consumption. An interesting approach has been to replace sugar with alternative sweeteners (AS), due to their impact on public health. Preclinical and clinical studies, which analyze the safety of AS intake, are still limited. Major pathogenic mechanisms of these substances include ROS and AGEs formation. Indeed, endothelial dysfunction involving in the pathogenesis of micro- and macro-vascular diseases is mitochondrial dysfunction dependent. Hyperglycemia and endoplasmic reticulum stress together produce ROS, contributing to the development and progression of cardiovascular complications during type 2 diabetes (T2D), thus causing oxidative changes and direct damage of lipids, proteins, and DNA. Epidemiological studies in healthy subjects have suggested that the consumption of artificial AS can promote CV complications, such as glucose intolerance and predisposition to the onset of T2D, whereas natural AS could reduce hyperglycemia, improve lipid metabolism and have antioxidant effects. Long-term prospective clinical randomized studies are needed to evaluate precisely whether exposure to alternative sugars can have clinical implications on natural history and clinical outcomes, especially in children or during the gestational period through breast milk.
Published:
2021-04
Title:
The Dual Role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification
Authors:
Mandatori, Domitilla; Pelusi, Letizia; Schiavone, Valeria; Pipino, Caterina; Di Pietro, Natalia; Pandolfi, Assunta
Abstract:
Osteoporosis (OP) and vascular calcification (VC) represent relevant health problems that frequently coexist in the elderly population. Traditionally, they have been considered independent processes, and mainly age-related. However, an increasing number of studies have reported their possible direct correlation, commonly defined as “bone-vascular crosstalk”. Vitamin K2 (VitK2), a family of several natural isoforms also known as menaquinones (MK), has recently received particular attention for its role in maintaining calcium homeostasis. In particular, VitK2 deficiency seems to be responsible of the so-called “calcium paradox” phenomenon, characterized by low calcium deposition in the bone and its accumulation in the vessel wall. Since these events may have important clinical consequences, and the role of VitK2 in bone-vascular crosstalk has only partially been explained, this review focuses on its effects on the bone and vascular system by providing a more recent literature update. Overall, the findings reported here propose the VitK2 family as natural bioactive molecules that could be able to play an important role in the prevention of bone loss and vascular calcification, thus encouraging further in-depth studies to achieve its use as a dietary food supplement.
Published:
2021-04
Title:
Executive summary: Updates to the dietary treatment of prediabetes and type 2 diabetes mellitus
Authors:
Pascual Fuster, V.; Pérez Pérez, A.; Carretero Gómez, J.; Caixàs Pedragós, A.; Gómez-Huelgas, R.; Pérez-Martínez, P.
Abstract:
Adequate lifestyle changes significantly reduce the cardiovascular risk factors associated with prediabetes and type 2 diabetes mellitus. Therefore, healthy eating habits, regular physical activity, abstaining from using tobacco, and good sleep hygiene are recommended for managing these conditions. There is solid evidence that diets that are plant-based; low in saturated fatty acids, cholesterol, and sodium; and high in fiber, potassium, and unsaturated fatty acids are beneficial and reduce the expression of cardiovascular risk factors in these subjects. In view of the foregoing, the Mediterranean diet, the DASH diet, a low-carbohydrate diet, and a vegan-vegetarian diet are of note. Additionally, the relationship between nutrition and these metabolic pathologies is fundamental in targeting efforts to prevent weight gain, reducing excess weight in the case of individuals with overweight or obesity; and personalizing treatment to promote patient empowerment. This document is the executive summary of an updated review that includes the main recommendations for improving dietary nutritional quality in people with prediabetes or type 2 diabetes mellitus. The full review is available on the webpages of the Spanish Society of Arteriosclerosis (SEA, for its initials in Spanish), the Spanish Diabetes Society (SED, for its initials in Spanish), and the Spanish Society of Internal Medicine (SEMI, for its initials in Spanish).
Published:
2021-03
Title:
Fructose Removal from the Diet Reverses Inflammation, Mitochondrial Dysfunction, and Oxidative Stress in Hippocampus
Authors:
Mazzoli, Arianna; Spagnuolo, Maria Stefania; Nazzaro, Martina; Gatto, Cristina; Iossa, Susanna; Cigliano, Luisa
Abstract:
Young age is often characterized by high consumption of processed foods and fruit juices rich in fructose, which, besides inducing a tendency to become overweight, can promote alterations in brain function. The aim of this study was therefore to (a) clarify brain effects resulting from fructose consumption in juvenile age, a critical phase for brain development, and (b) verify whether these alterations can be rescued after removing fructose from the diet. Young rats were fed a fructose-rich or control diet for 3 weeks. Fructose-fed rats were then fed a control diet for a further 3 weeks. We evaluated mitochondrial bioenergetics by high-resolution respirometry in the hippocampus, a brain area that is critically involved in learning and memory. Glucose transporter-5, fructose and uric acid levels, oxidative status, and inflammatory and synaptic markers were investigated by Western blotting and spectrophotometric or enzyme-linked immunosorbent assays. A short-term fructose-rich diet induced mitochondrial dysfunction and oxidative stress, associated with an increased concentration of inflammatory markers and decreased Neurofilament-M and post-synaptic density protein 95. These alterations, except for increases in haptoglobin and nitrotyrosine, were recovered by returning to a control diet. Overall, our results point to the dangerous effects of excessive consumption of fructose in young age but also highlight the effect of partial recovery by switching back to a control diet.
Published:
2021-03
Title:
Insulin-stimulated endoproteolytic TUG cleavage links energy expenditure with glucose uptake
Authors:
Habtemichael, Estifanos N.; Li, Don T.; Camporez, João Paulo; Westergaard, Xavier O.; Sales, Chloe I.; Liu, Xinran; López-Giráldez, Francesc; DeVries, Stephen G.; Li, Hanbing; Ruiz, Diana M.; Wang, Kenny Y.; Sayal, Bhavesh S.; González Zapata, Sofia; Dann, Pamela; Brown, Stacey N.; Hirabara, Sandro; Vatner, Daniel F.; Goedeke, Leigh; Philbrick, William; Shulman, Gerald I.; Bogan, Jonathan S.
Abstract:
TUG tethering proteins bind and sequester GLUT4 glucose transporters intracellularly, and insulin stimulates TUG cleavage to translocate GLUT4 to the cell surface and increase glucose uptake. This effect of insulin is independent of phosphatidylinositol 3-kinase, and its physiological relevance remains uncertain. Here we show that this TUG cleavage pathway regulates both insulin-stimulated glucose uptake in muscle and organism-level energy expenditure. Using mice with muscle-specific Tug (Aspscr1)-knockout and muscle-specific constitutive TUG cleavage, we show that, after GLUT4 release, the TUG C-terminal cleavage product enters the nucleus, binds peroxisome proliferator-activated receptor (PPAR)γ and its coactivator PGC-1α and regulates gene expression to promote lipid oxidation and thermogenesis. This pathway acts in muscle and adipose cells to upregulate sarcolipin and uncoupling protein 1 (UCP1), respectively. The PPARγ2 Pro12Ala polymorphism, which reduces diabetes risk, enhances TUG binding. The ATE1 arginyltransferase, which mediates a specific protein degradation pathway and controls thermogenesis, regulates the stability of the TUG product. We conclude that insulin-stimulated TUG cleavage coordinates whole-body energy expenditure with glucose uptake, that this mechanism might contribute to the thermic effect of food and that its attenuation could promote obesity.
Published:
2021-03
Title:
Low Carb and Ketogenic Diets Increase Quality of Life, Physical Performance, Body Composition, and Metabolic Health of Women with Breast Cancer
Authors:
Kämmerer, Ulrike; Klement, Rainer J.; Joos, Fabian T.; Sütterlin, Marc; Reuss-Borst, Monika
Abstract:
Breast cancer (BC) patients often ask for a healthy diet. Here, we investigated a healthy standard diet (SD), a low carb diet (LCD), and a ketogenic diet (KD) for BC patients during the rehabilitation phase. KOLIBRI was an open-label non-randomized one-site nutritional intervention trial, combining inpatient and outpatient phases for 20 weeks. Female BC patients (n = 152; mean age 51.7 years) could select their diet. Data collected were: Quality of life (QoL), spiroergometry, body composition, and blood parameters. In total 30, 92, and 30 patients started the KD, LCD, and SD, respectively. Of those, 20, 76, and 25 completed the final examination. Patients rated all diets as feasible in daily life. All groups enhanced QoL, body composition, and physical performance. LCD participants showed the most impressive improvement in QoL aspects. KD participants finished with a very good physical performance and muscle/fat ratio. Despite increased cholesterol levels, KD patients had the best triglyceride/high-density lipoprotein (HDL) ratio and homeostatic model assessment of insulin resistance index (HOMA-IR). Most metabolic parameters significantly improved in the LCD group. SD participants ended with remarkably low cholesterol levels but did not improve triglyceride/HDL or HOMA-IR. In conclusion, both well-defined KDs and LCDs are safe and beneficial for BC patients and can be recommended during the rehabilitation phase.
Published:
2021-03
Title:
Prey Size Decline as a Unifying Ecological Selecting Agent in Pleistocene Human Evolution
Authors:
Ben-Dor, Miki; Barkai, Ran
Abstract:
We hypothesize that megafauna extinctions throughout the Pleistocene, that led to a progressive decline in large prey availability, were a primary selecting agent in key evolutionary and cultural changes in human prehistory. The Pleistocene human past is characterized by a series of transformations that include the evolution of new physiological traits and the adoption, assimilation, and replacement of cultural and behavioral patterns. Some changes, such as brain expansion, use of fire, developments in stone-tool technologies, or the scale of resource intensification, were uncharacteristically progressive. We previously hypothesized that humans specialized in acquiring large prey because of their higher foraging efficiency, high biomass density, higher fat content, and the use of less complex tools for their acquisition. Here, we argue that the need to mitigate the additional energetic cost of acquiring progressively smaller prey may have been an ecological selecting agent in fundamental adaptive modes demonstrated in the Paleolithic archaeological record. We describe several potential associations between prey size decline and specific evolutionary and cultural changes that might have been driven by the need to adapt to increased energetic demands while hunting and processing smaller and smaller game.
Published:
2021-03
Title:
Type 2 Diabetes Prevention Focused on Normalization of Glycemia: A Two-Year Pilot Study
Authors:
McKenzie, Amy L.; Athinarayanan, Shaminie J.; McCue, Jackson J.; Adams, Rebecca N.; Keyes, Monica; McCarter, James P.; Volek, Jeff S.; Phinney, Stephen D.; Hallberg, Sarah J.
Abstract:
The purpose of this study is to assess the effects of an alternative approach to type 2 diabetes prevention. Ninety-six patients with prediabetes (age 52 (10) years; 80% female; BMI 39.2 (7.1) kg/m2) received a continuous remote care intervention focused on reducing hyperglycemia through carbohydrate restricted nutrition therapy for two years in a single arm, prospective, longitudinal pilot study. Two-year retention was 75% (72 of 96 participants). Fifty-one percent of participants (49 of 96) met carbohydrate restriction goals as assessed by blood beta-hydroxybutyrate concentrations for more than one-third of reported measurements. Estimated cumulative incidence of normoglycemia (HbA1c <5.7% without medication) and type 2 diabetes (HbA1c ≥6.5% or <6.5% with medication other than metformin) at two years were 52.3% and 3%, respectively. Prevalence of metabolic syndrome, class II or greater obesity, and suspected hepatic steatosis significantly decreased at two years. These results demonstrate the potential utility of an alternate approach to type 2 diabetes prevention, carbohydrate restricted nutrition therapy delivered through a continuous remote care model, for normalization of glycemia and improvement in related comorbidities.
Published:
2021-03
Title:
Acute responses of hepatic fat content to consuming fat, glucose and fructose alone and in combination in non-obese non-diabetic individuals with non-alcoholic fatty liver disease
Authors:
Kovar, J.; Dusilova, T.; Sedivy, P.; Bruha, R.; Gottfriedova, H.; Pavlikova, P.; Pitha, J.; Smid, V.; Drobny, M.; Dezortova, M.; Hajek, M.
Abstract:
We have recently demonstrated that a high-fat load can induce immediate increase in hepatic fat content (HFC) and that such an effect can be modified differently by co-administration of fructose or glucose in healthy subjects. Therefore, we addressed the question how consumption of these nutrients affects changes in HFC in subjects with non-alcoholic fatty liver disease (NAFLD). Eight male non-obese non-diabetic patients with NAFLD underwent 6 experiments each lasting 8 hours: 1. fasting, 2. high-fat load (150 g of fat (dairy cream) at time 0), 3. glucose (three doses of 50 g at 0, 2, and 4 hours), 4. high-fat load with three doses of 50 g of glucose, 5. fructose (three doses of 50 g at 0, 2, and 4 hours), 6. high-fat load with three doses of 50 g of fructose. HFC was measured using magnetic resonance spectroscopy prior to meal administration and 3 and 6 hours later. Plasma triglycerides, non-esterified fatty acids, glucose and insulin were monitored throughout each experiment. HFC increased by 10.4 ± 6.9% six hours after a high-fat load and by 15.2 ± 12.5% after high-fat load with fructose. When co-administering glucose with fat, HFC rose only transiently to return to baseline at 6 hours. Importantly, NAFLD subjects accumulated almost five times more fat in their livers than healthy subjects with normal HFC. Consumption of a high-fat load results in fat accumulation in the liver of NAFLD patients. Fat accumulation after a fat load is diminished by glucose but not fructose co-administration.
Published:
2021-02
Title:
Ardipithecus hand provides evidence that humans and chimpanzees evolved from an ancestor with suspensory adaptations
Authors:
Prang, Thomas C.; Ramirez, Kristen; Grabowski, Mark; Williams, Scott A.
Abstract:
The morphology and positional behavior of the last common ancestor of humans and chimpanzees are critical for understanding the evolution of bipedalism. Early 20th century anatomical research supported the view that humans evolved from a suspensory ancestor ...
Published:
2021-02
Title:
Effects of Two Months of Very Low Carbohydrate Ketogenic Diet on Body Composition, Muscle Strength, Muscle Area, and Blood Parameters in Competitive Natural Body Builders
Authors:
Paoli, Antonio; Cenci, Lorenzo; Pompei, PierLuigi; Sahin, Nese; Bianco, Antonino; Neri, Marco; Caprio, Massimiliano; Moro, Tatiana
Abstract:
Background: Ketogenic diet (KD) is a nutritional approach that restricts daily carbohydrates, replacing most of the reduced energy with fat, while maintaining an adequate quantity of protein. Despite the widespread use of KD in weight loss in athletes, there are still many concerns about its use in sports requiring muscle mass accrual. Thus, the present study sought to investigate the influence of a KD in competitive natural body builders. Methods: Nineteen volunteers (27.4 ± 10.5 years) were randomly assigned to ketogenic diet (KD) or to a western diet (WD). Body composition, muscle strength and basal metabolic rate were measured before and after two months of intervention. Standard blood biochemistry, testosterone, IGF-1, brain-derived neurotrophic factor (BDNF) and inflammatory cytokines (IL6, IL1β, TNFα) were also measured. Results: Body fat significantly decreased in KD (p = 0.030); whilst lean mass increased significantly only in WD (p < 0.001). Maximal strength increased similarly in both groups. KD showed a significant decrease of blood triglycerides (p < 0.001), glucose (p = 0.001), insulin (p < 0.001) and inflammatory cytokines compared to WD whilst BDNF increased in both groups with significant greater changes in KD (p < 0.001). Conclusions: KD may be used during body building preparation for health and leaning purposes but with the caution that hypertrophic muscle response could be blunted.
Published:
2021-02
Title:
Exploring late Paleolithic and Mesolithic diet in the Eastern Alpine region of Italy through multiple proxies
Authors:
Oxilia, Gregorio; Bortolini, Eugenio; Badino, Federica; Bernardini, Federico; Gazzoni, Valentina; Lugli, Federico; Romandini, Matteo; Radini, Anita; Terlato, Gabriele; Marciani, Giulia; Silvestrini, Sara; Sartorio, Jessica C. Menghi; Hohenstein, Ursula Thun; Fiorenza, Luca; Kullmer, Ottmar; Tuniz, Claudio; Cecchi, Jacopo Moggi; Talamo, Sahra; Fontana, Federica; Peresani, Marco; Benazzi, Stefano; Cristiani, Emanuela
Abstract:
The analysis of prehistoric human dietary habits is key for understanding the effects of paleoenvironmental changes on the evolution of cultural and social human behaviors. In this study, we compare results from zooarchaeological, stable isotope and dental ...
Published:
2021-02
Title:
Greater Loss of Central Adiposity from Low-Carbohydrate versus Low-Fat Diet in Middle-Aged Adults with Overweight and Obesity
Authors:
Garr Barry, Valene; Stewart, Mariah; Soleymani, Taraneh; Desmond, Renee A.; Goss, Amy M.; Gower, Barbara A.
Abstract:
The objective of this study is to determine whether middle-aged adults prescribed a low carbohydrate-high fat (LCHF) or low fat (LF) diet would have greater loss of central fat and to determine whether the insulin resistance (IR) affects intervention response. A total of 50 participants (52.3 ± 10.7 years old; 36.6 ± 7.4 kg/m2 BMI; 82% female) were prescribed either a LCHF diet (n = 32, carbohydrate: protein: fat of 5%:30%:65% without calorie restriction), or LF diet (n = 18, 63%:13–23%: 10–25% with calorie restriction of total energy expenditure—500 kcal) for 15 weeks. Central and regional body composition changes from dual-x-ray absorptiometry and serum measures were compared using paired t-tests and ANCOVA with paired contrasts. IR was defined as homeostatic model assessment (HOMA-IR) > 2.6. Compared to the LF group, the LCHF group lost more android (15.6 ± 11.2% vs. 8.3 ± 8.1%, p < 0.01) and visceral fat (18.5 ± 22.2% vs. 5.1 ± 15.8%, p < 0.05). Those with IR lost more android and visceral fat on the LCHF verses LF group (p < 0.05). Therefore, the clinical prescription to a LCHF diet may be an optimal strategy to reduce disease risk in middle-aged adults, particularly those with IR.
Published:
2021-02
Title:
Hypothalamic Renin–Angiotensin System and Lipid Metabolism: Effects of Virgin Olive Oil versus Butter in the Diet
Authors:
Segarra, Ana Belén; Domínguez-Vías, Germán; Redondo, José; Martínez-Cañamero, Magdalena; Ramírez-Sánchez, Manuel; Prieto, Isabel
Abstract:
The brain renin–angiotensin system (RAS) has been recently involved in the homeostatic regulation of energy. Our goal was to analyse the influence of a diet rich in saturated fatty acids (butter) against one enriched in monounsaturated fatty acids (olive oil) on hypothalamic RAS, and their relationship with the metabolism of fatty acids. Increases in body weight and visceral fat, together with an increase in aminopeptidase A expression and reductions in AngII and AngIV were observed in the hypothalamus of animals fed with the butter diet. In this group, a marked reduction in the expression of genes related to lipid metabolism (LPL, CD36, and CPT-1) was observed in liver and muscle. No changes were found in terms of body weight, total visceral fat and the expression of hepatic genes related to fatty acid metabolism in the olive oil diet. The expressions of LPL and CD36 were reduced in the muscles, although the decrease was lower than in the butter diet. At the same time, the fasting levels of leptin were reduced, no changes were observed in the hypothalamic expression of aminopeptidase A and decreases were noted in the levels of AngII, AngIV and AngIII. These results support that the type of dietary fat is able to modify the hypothalamic profile of RAS and the body energy balance, related to changes in lipid metabolism.
Published:
2021-02
Title:
Origins of modern human ancestry
Authors:
Bergström, Anders; Stringer, Chris; Hajdinjak, Mateja; Scerri, Eleanor M. L.; Skoglund, Pontus
Abstract:
New finds in the palaeoanthropological and genomic records have changed our view of the origins of modern human ancestry. Here we review our current understanding of how the ancestry of modern humans around the globe can be traced into the deep past, and which ancestors it passes through during our journey back in time. We identify three key phases that are surrounded by major questions, and which will be at the frontiers of future research. The most recent phase comprises the worldwide expansion of modern humans between 40 and 60 thousand years ago (ka) and their last known contacts with archaic groups such as Neanderthals and Denisovans. The second phase is associated with a broadly construed African origin of modern human diversity between 60 and 300 ka. The oldest phase comprises the complex separation of modern human ancestors from archaic human groups from 0.3 to 1 million years ago. We argue that no specific point in time can currently be identified at which modern human ancestry was confined to a limited birthplace, and that patterns of the first appearance of anatomical or behavioural traits that are used to define Homo sapiens are consistent with a range of evolutionary histories.
Published:
2021-02
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