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Title:
Neuroprotective mechanism altered by Alzheimer’s disease risk genes
Authors:
Abstract:
Gene variants associated with the risk of developing Alzheimer's disturb the brain's natural way of protecting itself against dementia.
Published:
January 7, 2022
Title:
Quelle alimentation proposer aux patients présentant une stéatohépatite non-alcoolique ?
Authors:
André-Dumont, Stéphanie I.; Lanthier, Nicolas
Abstract:
Résumé La maladie stéatosique du foie liée à une dysfonction métabolique (MAFLD) touche un quart de la population mondiale, dont certains d’entre eux évolueront vers une forme plus sévère appelée stéatohépatite non-alcoolique (NASH). Le principal facteur menant à cette pathologie est une alimentation déséquilibrée. Aucun traitement médicamenteux n’est reconnu à ce jour. Seule la prise en charge hygiénodiététique permet une amélioration des lésions histologiques de la NASH grâce à une perte de poids. Néanmoins, l’efficacité des régimes standards, la compliance des patients et la capacité à maintenir la perte de poids à long terme sont des difficultés fréquemment rencontrées. Dans cet article, nous analysons les données scientifiques récentes de différents types d’alimentation (régime méditerranéen, jeûne intermittent, régime cétogène) permettant d’apporter des bénéfices hépatiques et parfois extrahépatiques. Les inconvénients ou limites possibles sont également discutés. Le bénéfice éventuel d’autres stratégies nutritionnelles (café, acides gras oméga-3, polyphénols…) est finalement présenté. Le changement de mode alimentaire peut, dès lors, être adapté aux attentes du patient et occasionner des bénéfices indépendamment de la perte de poids. Metabolic dysfunction-associated fatty liver disease (MAFLD) affects a quarter of the world's population, some of whom will progress to a more severe form called non-alcoholic steatohepatitis (NASH). The main factor leading to this condition is an unbalanced diet. No drug treatment is approved to date and only dietary management can improve the histological lesions of NASH through weight loss. However, the efficacy of standard diets, patient compliance and the ability to maintain weight loss over the long term are common difficulties. In this review, we analyze recent scientific data on different types of diet (Mediterranean diet, intermittent fasting, ketogenic diet), which can bring benefits on general and liver health. Drawbacks or limitations are also listed. The possible benefit of other nutritional strategies (coffee consumption, omega-3, polyphenols…) is discussed. The value of dietary change could be tailored to the patient's needs without necessarily imposing an intense weight loss.
Published:
January 7, 2022
Title:
Effect of a dietary intervention including minimal and unprocessed foods, high in natural saturated fats, on the lipid profile of children, pooled evidence from randomized controlled trials and a cohort study
Authors:
Hendriksen, Rosanne Barbra; Gaag, Ellen José van der
Abstract:
Aim To study the possible effects of a dietary intervention with minimal and unprocessed foods, high in natural saturated fats on the lipid profile and body mass index of children. Method This study combines three intervention studies; one non-randomized retrospective cohort study and two randomized controlled trials, to a pooled analysis. The intervention group received a dietary intervention of minimal and unprocessed foods for three to six months, consisting of five times per week green vegetables, three times per week beef, daily 200–300 mL whole cow’s milk (3.4% fat) and whole dairy butter (80% fat) on each slice of bread. The control group continued their usual dietary habits. Raw data of the three intervention studies where combined into one single dataset for data analysis, using mixed effects analysis of covariance to test the effects of the dietary advice on the main study outcomes, which are measurements of the lipid profile. Results In total, 267 children aged 1 to 16 years were followed. 135 children were included in the intervention group and 139 children in the control group. Characteristics (age, gender and follow-up period) were equally distributed between the groups at baseline. In the intervention group HDL-cholesterol increased significantly from 1.22 mmol/L, 95% confidence interval (CI) 1.14–1.32 to 1.42 mmol/L 95% CI 1.30–1.65 (p = 0.007). The increase over time in HDL cholesterol in the intervention group was significantly different compared to the increase in the control group (from 1.26 mmol/L, 95% CI 1.19–1.35, to 1.30 mmol/L, 95% CI 1.26–1.37) (p = 0.04). Due to the increased HDL concentration in the intervention group, the total cholesterol/HDL cholesterol ratio decreased significantly from 3.70 mmol/L, 95% CI 3.38–3.87, to 3.25 mmol/L, 95% CI 2.96–3.31 (p = 0.05). Conclusion Consumption of minimal and unprocessed foods (high in natural saturated fats) has favourable effects on HDL cholesterol in children. Therefore, this dietary advice can safely be recommended to children.
Published:
January 5, 2022
Title:
High versus low-added sugar consumption for the primary prevention of cardiovascular disease
Authors:
Bergwall, Sara; Johansson, Anna; Sonestedt, Emily; Acosta, Stefan
Abstract:
BACKGROUND: High intake of added sugar have been suggested to impact the risk for cardiovascular disease (CVD). Knowledge on the subject can contribute to preventing CVD. OBJECTIVES: To assess the effects of a high versus low-added sugar consumption for primary prevention of CVD in the general population. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, Conference Proceedings Citation Index-Science (CPCI-S) on 2 July 2021. We also conducted a search of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) Search Portal for ongoing or unpublished trials. The search was performed together with reference checking, citation searching and contact with study authors to identify additional studies. We imposed no restriction on language of publication or publication status. SELECTION CRITERIA: We included randomised controlled trials (RCTs), including cross-over trials, that compared different levels of added sugar intake. Exclusion criteria were: participants aged below 18 years; diabetes mellitus (type 1 and 2); and previous CVD. Primary outcomes were incident cardiovascular events (coronary, carotid, cerebral and peripheral arterial disease) and all-cause mortality. Secondary outcomes were changes in systolic and diastolic blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting plasma glucose and adverse events (gastrointestinal symptoms and impaired dental health). DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 21 RCTs (1110 participants completing the interventions) examining the effects of different levels of added sugar intake with a mean duration of 14 weeks. The study participants were generally described as healthy and the mean age ranged from 22 to 57 years. No studies reported on cardiovascular events or all-cause mortality. There was minimal effect of low intake of added sugar on total cholesterol levels (MD 0.11, 95% CI 0.01 to 0.21; I² = 0%; 16 studies; 763 participants; low certainty of evidence) and triglycerides (MD 0.10, 95% CI 0.03 to 0.17; I² = 3%; 14 studies; 725 participants) but no evidence of effect on LDL-cholesterol and HDL-cholesterol. There was minimal effect on diastolic blood pressure (MD 1.52, 95% CI 0.67 to 2.37; I² = 0%; 13 studies; 873 participants) and on systolic blood pressure (MD 1.44, 95% 0.08 to 2.80; I² = 27%, 14 studies; 873 participants; low certainty of evidence), but no evidence of effect on fasting plasma glucose. Only one study reported on dental health, with no events. No other trials reported adverse events (impaired dental health or gastrointestinal symptoms). All results were judged as low-quality evidence according to GRADE. The risk of bias was generally unclear, five studies were classified at an overall low risk of bias (low risk in at least four domains, not including other bias). AUTHORS' CONCLUSIONS: No trials investigating the effect of added sugar on cardiovascular events or all-cause mortality were identified in our searches. Evidence is uncertain whether low intake of added sugar has an effect on risk factors for CVD; the effect was small and the clinical relevance is, therefore, uncertain. Practical ways to achieve reductions in dietary added sugar includes following current dietary recommendations. Future trials should have longer follow-up time and report on all-cause mortality and cardiovascular events in order to clarify the effect of added sugar on these outcomes. Future trials should also aim for more direct interventions and preferably be more independent of industry funding.
Published:
January 5, 2022
Title:
Is autosomal dominant polycystic kidney disease an early sweet disease?
Authors:
Dachy, Angélique; Decuypere, Jean-Paul; Vennekens, Rudi; Jouret, François; Mekahli, Djalila
Abstract:
The clinical course of autosomal dominant polycystic kidney disease (ADPKD) starts in childhood. Evidence of the beneficial impact of early nephron-protective strategies and lifestyle modifications on ADPKD prognosis is accumulating. Recent studies have described the association of overweight and obesity with rapid disease progression in adults with ADPKD. Moreover, defective glucose metabolism and metabolic reprogramming have been reported in distinct ADPKD models highlighting these pathways as potential therapeutic targets in ADPKD. Several “metabolic” approaches are currently under evaluation in adults, including ketogenic diet, food restriction, and metformin therapy. No data are available on the impact of these approaches in childhood thus far. Yet, according to World Health Organization (WHO), we are currently facing a childhood obesity crisis with an increased prevalence of overweight/obesity in the pediatric population associated with a cardio-metabolic risk profile. The present review summarizes the knowledge about the role of glucose metabolism in the pathophysiology of ADPKD and underscores the possible harm of overweight and obesity in ADPKD especially in terms of long-term cardiovascular outcomes and renal prognosis.
Published:
January 5, 2022
Title:
Replacing dietary carbohydrates and refined grains with different alternatives and risk of cardiovascular diseases in a multi-ethnic Asian population
Authors:
Lim, Charlie G Y; Tai, E Shyong; van Dam, Rob M
Abstract:
Cardiovascular diseases (CVDs) are a major cause of deaths worldwide, but prospective data on dietary risk factors for CVD in South and Southeast Asian populations are sparse.We aimed to evaluate the relation between macronutrient and food intakes and incidence of major adverse cardiovascular events (MACEs) in a multi-ethnic Asian population.We used data from the Singapore Multi-Ethnic Cohort (n = 12,408), a prospective cohort of ethnic Chinese, Malay, and Indian adults aged 21‒65 y recruited between 2004 and 2010. Dietary intakes were assessed using a validated food-frequency questionnaire, and the incidence of MACEs was ascertained through data linkage with national registries. A Cox proportional hazards model was used to evaluate the associations between dietary intakes and MACE risk.Over a mean (SD) follow-up of 10.1 (2.3) y, 746 incident cases of MACEs were documented. We observed a direct association between carbohydrate intake and MACE risk (highest vs. lowest quartile, HR: 1.35; 95% CI: 1.07, 1.71; P-trend = 0.001). Replacing 5% of energy from carbohydrate with polyunsaturated fat (HR: 0.79; 95% CI: 0.69, 0.91) but not saturated fat (HR: 0.95; 95% CI: 0.84, 1.09) was significantly associated with a lower MACE risk. In terms of food groups, replacing 1 serving/d of refined grains with fruit (HR: 0.93; 95% CI: 0.87, 0.99), vegetables (HR: 0.92; 95% CI: 0.85, 1.00), and dairy (HR: 0.90; 95% CI: 0.82, 0.98) was associated with lower MACE risk. Cholesterol intake was associated with a higher MACE risk in ethnic Indians (highest vs. lowest quartile, HR: 2.40; 95% CI: 1.53, 3.75; P-trend < 0.001) but not in ethnic Malay or Chinese (P-interaction = 0.015).Moderating carbohydrate intakes by increasing polyunsaturated fat intake and replacing refined grains with fruits, vegetables, and dairy was associated with lower MACE risk in Asian populations.
Published:
January 5, 2022
Title:
Fasting Induces a Highly Resilient Deep Quiescent State in Muscle Stem Cells via Ketone Body Signaling
Authors:
Benjamin, Daniel I.; Both, Pieter; Benjamin, Joel S.; Nutter, Christopher W.; Tan, Jenna H.; Kang, Jengmin; Machado, Leo A.; Klein, Julian D. D.; Morree, Antoine de; Kim, Soochi; Liu, Ling; Dulay, Hunter; Feraboli, Ludovica; Louie, Sharon M.; Nomura, Daniel K.; Rando, Thomas A.
Abstract:
Short-term fasting is beneficial for the regeneration of multiple tissue types. However, the effects of fasting on muscle regeneration are largely unknown. Here we report that fasting slows muscle repair both immediately after the conclusion of fasting as well as after multiple days of refeeding. We show that ketosis, either endogenously produced during fasting or a ketogenic diet, or exogenously administered, promotes a deep quiescent state in muscle stem cells (MuSCs). Although deep quiescent MuSCs are less poised to activate, slowing muscle regeneration, they have markedly improved survival when facing sources of cellular stress. Further, we show that ketone bodies, specifically β-hydroxybutyrate, directly promote MuSC deep quiescence via a non-metabolic mechanism. We show that β-hydroxybutyrate functions as an HDAC inhibitor within MuSCs leading to acetylation and activation of an HDAC1 target protein p53. Finally, we demonstrate that p53 activation contributes to the deep quiescence and enhanced resilience observed during fasting.
Published:
January 4, 2022
Title:
The energy balance hypothesis of obesity: do the laws of thermodynamics explain excessive adiposity?
Authors:
Torres-Carot, Vicente; Suárez-González, Andrés; Lobato-Foulques, Cecilia
Abstract:
In this work, we reflect upon the energy balance hypothesis of obesity. International organizations, the general population and many scientists hold the belief that obesity is indisputably caused by an imbalance between energy intake and energy expenditure. Most of them argue that the laws of thermodynamics support this view. We identify and review the main arguments used to support this belief, and we explain the reasoning mistakes those arguments harbor. We show that the laws of thermodynamics do not support the idea that obesity is an energy problem nor an energy balance problem more than they do in the growth of any other tissue in the human body. We argue that the validity of the energy balance paradigm for obesity must be questioned. Although correction of a wrong belief is laudable per se, in this particular case harm may arise by influencing the way in which obesity prevention is tackled and obese patients are treated.
Published:
January 4, 2022
Title:
The energy balance hypothesis of obesity: do the laws of thermodynamics explain excessive adiposity?
Authors:
Torres-Carot, Vicente; Suárez-González, Andrés; Lobato-Foulques, Cecilia
Abstract:
In this work, we reflect upon the energy balance hypothesis of obesity. International organizations, the general population and many scientists hold the belief that obesity is indisputably caused by an imbalance between energy intake and energy expenditure. Most of them argue that the laws of thermodynamics support this view. We identify and review the main arguments used to support this belief, and we explain the reasoning mistakes those arguments harbor. We show that the laws of thermodynamics do not support the idea that obesity is an energy problem nor an energy balance problem more than they do in the growth of any other tissue in the human body. We argue that the validity of the energy balance paradigm for obesity must be questioned. Although correction of a wrong belief is laudable per se, in this particular case harm may arise by influencing the way in which obesity prevention is tackled and obese patients are treated.
Published:
January 4, 2022
Title:
Ketogenic diet ameliorates lipid dysregulation in type 2 diabetic mice by downregulating hepatic pescadillo 1
Authors:
Zhou, Jielin; Lu, Yao; Jia, Yajing; Lu, Jing; Jiang, Zhengxuan; Chen, Keyang
Abstract:
BACKGROUND: Previous reports implied a possible link between PES1 and lipid metabolism. However, the role of PES1 in regulating T2DM related lipid metabolism and the effect of ketogenic diet (KD) on PES1 have not been reported. The aim of present study is to explore the role of PES1 in effects of KD on diabetic mice and its mediated mechanism. METHODS: Male C57BL/6J and KKAy mice were fed with standard diet (SD) and KD, respectively. Simultaneously, McArdle 7777 cells were treated by β-hydroxybutyric acid (β-HB), Pes1 siRNA or Pes1 overexpression plasmid, respectively. Additionally, liver-conditional knockout (CKO) of Pes1 in vivo was applied. RESULTS: Hepatic PES1 expression in diabetic mice was markedly increased, which was suppressed by KD feeding with an accompanying reduction of hepatic and plasma triglycerides (TG). In mice with CKO of Pes1, the protein levels of p300, SREBP1c, FASN, SCD1, Caspase1, NLRP3 and GSDMD were dramatically downregulated in livers, and the plasma and hepatic TG, IL-1β and IL-18 were decreased as well. The similar outcomes were also observed in β-HB and Pes1 knockdown treated hepatocytes. By contrast, Pes1 overexpression in cultured hepatocytes showed that these levels were significantly enhanced, which were, however reduced under β-HB treatment. Mechanistically, we discovered that β-HB decreased CHOP binding to the Pes1 promoters, resulting in the downregulation of PES1, thereby reducing PES1 binding to p300 and Caspase1 promoters. The inhibition of p300 and Caspase1 expression elicited the dramatic suppression of acetylation of SREBP1c via its interaction with p300, and the decreased GSDMD levels. Besides, knockdown of Caspase1 also alleviated the TG levels in cultured hepatocytes. CONCLUSION: KD may improve lipid dysregulation in type 2 diabetic mice by downregulating hepatic PES1 expression.
Published:
January 3, 2022
Title:
Severe Hypertriglyceridemia-Induced Necrotizing Pancreatitis Associated With Ketogenic Diet in a Well-Controlled Patient With Type 2 Diabetes Mellitus
Authors:
Chan, Jacqueline T.; Mude, Pooja J.; Canfield, Whitney; Makhija, Jinal; Yap, John Erikson L.
Abstract:
The ketogenic diet (keto diet) has become an increasingly popular approach for both weight loss and as an alternative diet for type 2 diabetes mellitus (T2DM). Owing to the nature of the keto diet, patients are at risk of developing hypertriglyceridemia (HTG) due to the high amount of triglycerides consumed by individuals during the initiation of this diet. Acute pancreatitis can result from HTG. We present a case of a 19-year-old African American male with well-controlled T2DM and no history of HTG who developed severe necrotizing HTG-induced pancreatitis after an unsupervised three-month trial of the keto diet.
Published:
January 2, 2022
Title:
COVID-19 pandemic and weight gain in American adults: A nationwide population-based study
Authors:
Khubchandani, Jagdish; Price, James H.; Sharma, Sushil; Wiblishauser, Michael J.; Webb, Fern J.
Abstract:
Background The COVID-19 pandemic has affected the lives of people in many ways. However, little is known about weight gain in American adults during the pandemic. Aims and methods The purpose of this study was to conduct a national assessment of weight gain in adult Americans after the first year of the pandemic. An online questionnaire was employed to explore perceptions of adults regarding pandemic weight gain and the relationship between weight gain and sociodemographic characteristics, pre-pandemic weight status, and psychological distress. Multiple methods were used to assess the psychometric properties of the questionnaire (i.e., face validity, content validity, and internal consistency reliability testing). Chi-Square tests and logistic regression analysis were used to assess group differences and predictors of weight gain in the study participants. Results A total of 3,473 individuals participated in the study with weight changes distributed as: gained weight (48%), remained the same weight (34%), or lost weight (18%). Those who reported being very overweight before the pandemic were most likely to gain weight (65%) versus those who reported being slightly overweight (58%) or normal weight (40%) before the pandemic. Weight gain was statistically significantly higher in those with anxiety (53%), depression (52%), or symptoms of both (52%). The final multiple regression model found that the statistically significant predictors of pandemic weight gain were psychological distress, pre-pandemic weight status, having children at home; and time since last bodyweight check. Conclusions Population health promotion strategies in the pandemic should emphasize stress reduction to help individuals manage body weight and avoid chronic diseases in the future.
Published:
January 1, 2022
Title:
Can the ketogenic diet lead to Wernicke’s encephalopathy?
Authors:
Javaid, Simra; Lindenberg, Amanda; Srinivasan, Rajashree
Abstract:
BACKGROUND: Wernicke’s encephalopathy (WE), a neurological disorder due to the deficiency of thiamine, is often underdiagnosed in the pediatric population. The classic triad of mental status changes, oculomotor abnormality, and ataxia is observed in
Published:
January 1, 2022
Title:
Early Pleistocene hominin subsistence behaviors in South Africa: Evidence from the hominin-bearing deposit of Cooper's D (Bloubank Valley, South Africa)
Authors:
Hanon, Raphaël; Patou-Mathis, Marylène; Péan, Stephane; Prat, Sandrine; Cohen, Brigette F.; Steininger, Christine
Abstract:
Evidence of the consumption of meat through hunting or scavenging by Early Pleistocene hominins is scarce, particularly in South Africa. Moreover, the interpretations of taphonomic evidence are subject to an important discussion commonly called the ‘hunting-vs-scavenging debate.’ Until today, only the Swartkrans Members 1–3 site has yielded a butchered bone assemblage large enough to permit reconstruction of carcass acquisition strategies by Early Pleistocene hominins in South Africa. This leaves an information gap between 1.4 and 1.0 Ma. Here, we provide the first evidence of meat consumption by hominins during this gap, based on the zooarchaeological study of the large mammal bone assemblage recovered from the Cooper's D site, South Africa. Based on skeletal part representation, our results show density-mediated attrition of bovid bones due to predepositional and postdepositional destruction. We argue that this attrition is the result of both abiotic (i.e., decalcification) and biotic (i.e., carnivore ravaging) processes. Bovid mortality profiles point out the involvement of ambush predators such as large felids. Bone surface modifications also indicate that the assemblage has been accumulated mostly by carnivores but with some hominin involvement as well. We observe all the stages of animal carcass processing (skinning, disarticulation, defleshing, marrow extraction) as well as the exploitation of a diversity of prey size classes at both Swartkrans Members 1–3 and Cooper's D. Thus, our study shows the importance of the Cooper's D bone assemblage for understanding Early Pleistocene hominin subsistence behaviors. Moreover, this article highlights the need for including long bone flake specimens in the analysis of large bone assemblages from South African caves to better understand the Early Pleistocene hominin bone damage record.
Published:
January 1, 2022
Title:
Efficacy of the Ketogenic Diet for Pediatric Epilepsy According to the Presence of Detectable Somatic mTOR Pathway Mutations in the Brain
Authors:
Ko, Ara; Sim, Nam Suk; Choi, Han Som; Yang, Donghwa; Kim, Se Hee; Lee, Joon Soo; Kim, Dong Seok; Lee, Jeong Ho; Kim, Heung Dong; Kang, Hoon-Chul
Abstract:
Ko A, et al. J Clin Neurol. 2022 Jan;18(1):71-78. https://doi.org/10.3988/jcn.2022.18.1.71
Published:
January 1, 2022
Title:
Plant bedding construction between 60,000 and 40,000 years ago at Border Cave, South Africa
Authors:
Sievers, Christine; Backwell, Lucinda; Francesco d’Errico; Wadley, Lyn
Abstract:
Extraordinary preservation of plant remains provides an insight into the construction and materials of bedding at Border Cave, South Africa. Towards the back of the cave there are particularly thick layers of desiccated and charred grass and our botanical study is from bulk samples of these approximately 60,000 to 40,000 year-old layers (Members 3 BS, 2 WA, 2 BS and 1 BS Lower C). More than one type of panicoid grass was identified, sedge nutlets were present in the older layers and in Member 2 WA particularly, eudicotyledon leaves were preserved. Plant bedding construction may have altered slightly over time with the use of sedges decreasing in favour of grass. A small item that appears to be woven monocotyledon leaf blades was recovered from Member 1 BS Lower C (42,600 years old), potentially making it the oldest evidence of simple weaving. The bedding is generally desiccated rather than burned, and often lies on an ash base. It is possible that the site's occupants burned old bedding to provide an ash base for fresh bedding. The unique preservation of desiccated plant material from as early as 60,000 years ago may in part be due to these ashy surfaces.
Published:
January 1, 2022
Title:
Reconstructing Neanderthal diet: The case for carbohydrates
Authors:
Hardy, Karen; Bocherens, Hervé; Miller, Jennie Brand; Copeland, Les
Abstract:
Evidence for plants rarely survives on Paleolithic sites, while animal bones and biomolecular analyses suggest animal produce was important to hominin populations, leading to the perspective that Neanderthals had a very-high-protein diet. But although individual and short-term survival is possible on a relatively low-carbohydrate diet, populations are unlikely to have thrived and reproduced without plants and the carbohydrates they provide. Today, nutritional guidelines recommend that around half the diet should be carbohydrate, while low intake is considered to compromise physical performance and successful reproduction. This is likely to have been the same for Paleolithic populations, highlighting an anomaly in that the basic physiological recommendations do not match the extensive archaeological evidence. Neanderthals had large, energy-expensive brains and led physically active lifestyles, suggesting that for optimal health they would have required high amounts of carbohydrates. To address this anomaly, we begin by outlining the essential role of carbohydrates in the human reproduction cycle and the brain and the effects on physical performance. We then evaluate the evidence for resource availability and the archaeological evidence for Neanderthal diet and investigate three ways that the anomaly between the archaeological evidence and the hypothetical dietary requirements might be explained. First, Neanderthals may have had an as yet unidentified genetic adaptation to an alternative physiological method to spare blood glucose and glycogen reserves for essential purposes. Second, they may have existed on a less-than-optimum diet and survived rather than thrived. Third, the methods used in dietary reconstruction could mask a complex combination of dietary plant and animal proportions. We end by proposing that analyses of Paleolithic diet and subsistence strategies need to be grounded in the minimum recommendations throughout the life course and that this provides a context for interpretation of the archaeological evidence from the behavioral and environmental perspectives.
Published:
January 1, 2022
Title:
Calorie Restriction for Cancer Prevention and Therapy: Mechanisms, Expectations, and Efficacy
Authors:
Vidoni, Chiara; Ferraresi, Alessandra; Esposito, Andrea; Maheshwari, Chinmay; Dhanasekaran, Danny N.; Mollace, Vincenzo; Isidoro, Ciro
Abstract:
Chiara Vidoni, Alessandra Ferraresi, Andrea Esposito, Chinmay Maheshwari, Danny N. Dhanasekaran, Vincenzo Mollace, Ciro Isidoro. J Cancer Prev 2021;26:224-36. https://doi.org/10.15430/JCP.2021.26.4.224
Published:
December 30, 2021
Title:
Clinical course of the longest-lived man in the world: A case report
Authors:
Shikimoto, Ryo; Arai, Yasumichi; Yuasa, Shinsuke; Gondo, Yasuyuki; Yasumoto, Saori; Abe, Yukiko; Hirose, Nobuyoshi
Abstract:
BACKGROUND AND OBJECTIVE: Supercentenarians, people who have reached 110 years of age, represent an ultimate model of human longevity. We have conducted research from both biomedical and psychosocial perspectives to clarify the factors that contribute to healthy longevity. The current study described the clinical course of the oldest lived man in the world. METHODS: Kimura Jiroemon, who is the verified oldest man in recorded history, lived for more than 116 years. We conducted a longitudinal investigation including physical and psychological assessments, blood data, and electrocardiogram (ECG) from the age of 111 and obtained medical data such as computed tomography (CT) images during the course of hospitalizations in the last year of his life. RESULTS: At the age of 111, Jiroemon was almost independent regarding activities of daily living. Additionally, his Philadelphia Geriatric Center Morale Scale score was 15/17, indicating high psychological well-being. His biological data included first-degree atrioventricular (AV) block on ECG; mild decreases of hemoglobin (11.6 g/dL), hematocrit (36.2%), and albumin levels (3.5 g/dL); and elevated serum cystatin C levels (1.32 mg/L), indicating potential dysfunction of the renal and electrical conduction systems. He then lived without fatal illness until the age of 115 years. At this age, he lost consciousness, and his ECG revealed complete AV block. At the first hospitalization for intensive examination, his doctor recommended implanting a cardiac pacemaker, but he and his family declined. On December 12, 2012, his condition rapidly worsened, and he was hospitalized twice for heart failure because of AV block. On May 11, 2013, he lost consciousness after breakfast, and he was hospitalized for the fourth time. He was diagnosed with pneumonia and heart failure based on his chest CT findings and elevated brain natriuretic peptide levels (160 pg/mL), and died on June 12, 2013 at the age of 116. CONCLUSIONS: Despite having no cardiovascular risk factors throughout his life, Jiroemon developed heart failure from potential heart and kidney dysfunction, suggesting that aging of the cardiorenal system was the ultimate pathology of the oldest man in the world. His clinical course represents a model of both suppression of morbidity and extreme longevity. Comprehensive health and longevity research studies from physical and psychological aspects are required.
Published:
December 30, 2021
Title:
Impact of ketogenic diet and ketone diester supplementation on body weight, blood glucose, and ketones in Sprague Dawley rats fed over two weeks
Authors:
Modica, LT Claire M.; Flores-Felix, Krystal; Casachahua, LT John D.; Asquith, Paul; Tschiffely, Anna; Ciarlone, Stephanie; Ahlers, Stephen T.
Abstract:
Ketogenic diets consist of low carbohydrate/high fat, shifting energy reliance from glucose to ketone bodies. Ketone diester supplement to a standard diet (ketone ester) increases ketone bodies by adding a substance without altering other consumed foods. We evaluated weight, glucose, and ketone concentrations in rats fed ketogenic diet and ketone ester feeds. We hypothesized that these feeds would increase ketones and decrease glucose and weight. We tested 16 male and 16 female Sprague Dawley rats randomly assigned to standard diet, ketogenic diet, or ketone ester for two weeks. Weight and blood glucose and ketones were measured daily. Group means were compared by analysis of variance. Ketogenic diet and ketone ester both increased ketones and decreased weight compared to standard diet (p
Published:
December 30, 2021
Title:
Losing sleep by staying up late leads adolescents to consume more carbohydrates and a higher glycemic load
Authors:
Duraccio, Kara McRae; Whitacre, Catharine; Krietsch, Kendra N.; Zhang, Nanhua; Summer, Suzanne; Price, Morgan; Saelens, Brian E.; Beebe, Dean W.
Abstract:
This study examined how short sleep impacts dietary consumption in adolescents by testing whether experimentally shortening sleep influences the amount, macronutrient content, food types, and timing of food consumed. Ninety-three adolescents completed a within-subjects crossover paradigm comparing five nights of short sleep (6.5-hour sleep opportunity) to five nights of Healthy Sleep (9.5-hour sleep opportunity). Within each condition, adolescents completed three multiple-pass dietary recalls that recorded the types, amount, and timing of food intake. The following outcomes were averaged across days of dietary recall within condition: kilocalories, grams of carbohydrates, fat, protein, and added sugars, glycemic load of foods, and servings of specific types of foods (low-calorie drinks, sweetened drinks, fruits/vegetables, meats/proteins, processed snacks, "fast food" entrees, grains, and sweets/desserts). Timing of consumption of kilocalorie and macronutrient outcomes were also examined across four noncumulative time bins: 06:00-10:59, 11:00-15:59, 16:00-20:59, and 21:00-01:00. Adolescents slept 2 h and 20 min longer in Healthy Sleep than in Short Sleep (p
Published:
December 17, 2021
Title:
Acetoacetate protects macrophages from lactic acidosis-induced mitochondrial dysfunction by metabolic reprograming
Authors:
Adam, Clément; Paolini, Léa; Gueguen, Naïg; Mabilleau, Guillaume; Preisser, Laurence; Blanchard, Simon; Pignon, Pascale; Manero, Florence; Le Mao, Morgane; Morel, Alain; Reynier, Pascal; Beauvillain, Céline; Delneste, Yves; Procaccio, Vincent; Jeannin, Pascale
Abstract:
Lactic acidosis, the extracellular accumulation of lactate and protons, is a consequence of increased glycolysis triggered by insufficient oxygen supply to tissues. Macrophages are able to differentiate from monocytes under such acidotic conditions, and remain active in order to resolve the underlying injury. Here we show that, in lactic acidosis, human monocytes differentiating into macrophages are characterized by depolarized mitochondria, transient reduction of mitochondrial mass due to mitophagy, and a significant decrease in nutrient absorption. These metabolic changes, resembling pseudostarvation, result from the low extracellular pH rather than from the lactosis component, and render these cells dependent on autophagy for survival. Meanwhile, acetoacetate, a natural metabolite produced by the liver, is utilized by monocytes/macrophages as an alternative fuel to mitigate lactic acidosis-induced pseudostarvation, as evidenced by retained mitochondrial integrity and function, retained nutrient uptake, and survival without the need of autophagy. Our results thus show that acetoacetate may increase tissue tolerance to sustained lactic acidosis.
Published:
December 8, 2021
Title:
Statin Use Is Associated With Diabetes Progression
Authors:
Slomski, Anita
Abstract:
A recent observational study suggests that people with diabetes who use statins experience a greater rate of diabetes progression than those who don’t use the drugs.The retrospective study of US patients in the Veterans Affairs health system included 83 022 pairs of statin users and active comparators who used a histamine-2 receptor blocker or proton pump inhibitor but not statins. The diabetes progression composite outcome included new insulin initiation, increase in the number of glucose-lowering medication classes prescribed, 5 or more blood glucose measurements of 200 mg/dL or greater, or a new diagnosis of ketoacidosis or uncontrolled diabetes.
Published:
December 7, 2021
Title:
Statin Use Is Associated With Diabetes Progression
Authors:
Slomski, Anita
Abstract:
A recent observational study suggests that people with diabetes who use statins experience a greater rate of diabetes progression than those who don’t use the drugs.The retrospective study of US patients in the Veterans Affairs health system included 83 022 pairs of statin users and active comparators who used a histamine-2 receptor blocker or proton pump inhibitor but not statins. The diabetes progression composite outcome included new insulin initiation, increase in the number of glucose-lowering medication classes prescribed, 5 or more blood glucose measurements of 200 mg/dL or greater, or a new diagnosis of ketoacidosis or uncontrolled diabetes.
Published:
December 7, 2021
Title:
Treatments for skeletal muscle abnormalities in heart failure: sodium-glucose transporter 2 and ketone bodies
Authors:
Takada, Shingo; Sabe, Hisataka; Kinugawa, Shintaro
Abstract:
Various skeletal muscle abnormalities are known to occur in heart failure (HF), and are closely associated with exercise intolerance. Particularly, abnormal energy metabolism caused by mitochondrial dysfunction in skeletal muscle is a cause of decreased endurance exercise capacity. However, to date, no specific drug treatment has been established for the skeletal muscle abnormalities and exercise intolerance occurring in HF patients. Sodium-glucose transporter 2 (SGLT2) inhibitors promote glucose excretion by suppressing glucose reabsorption in the renal tubules, which has a hypoglycemic effect independent of insulin secretion. Recently, large clinical trials have demonstrated that treatment with SGLT2 inhibitors suppresses cardiovascular events in patients who have HF with systolic dysfunction. Mechanisms of the therapeutic effects of SGLT2 inhibitors for HF have been suggested to be diuretic, suppression of neurohumoral factor activation, renal protection, and improvement of myocardial metabolism, but has not been clarified to date. SGLT2 inhibitors are known to increase blood ketone bodies. This suggests that they may improve the abnormal skeletal muscle metabolism in HF, i.e., improve fatty acid metabolism, suppress glycolysis, and utilize ketone bodies in mitochondrial energy production. Ultimately, they may improve aerobic metabolism in skeletal muscle, and suppress anaerobic metabolism and improve aerobic exercise capacity at the level of the anaerobic threshold. The potential actions of such SGLT2 inhibitors explain their effectiveness in HF, and may be candidates for new drug treatments aimed at improving exercise intolerance. In this review, we outlined the effects of SGLT2 inhibitors on skeletal muscle metabolism, with a particular focus on ketone metabolism.
Published:
December 3, 2021
Title:
Behavioral Characteristics and Self-Reported Health Status among 2029 Adults Consuming a “Carnivore Diet”
Authors:
Lennerz, Belinda S; Mey, Jacob T; Henn, Owen H; Ludwig, David S
Abstract:
The “carnivore diet,” based on animal foods and excluding most or all plant foods, has attracted recent popular attention. However, little is known about the health effects and tolerability of this diet, and concerns for nutrient deficiencies and cardiovascular disease risk have been raised.We obtained descriptive data on the nutritional practices and health status of a large group of carnivore diet consumers.A social media survey was conducted 30 March–24 June, 2020 among adults self-identifying as consuming a carnivore diet for ≥6 mo. Survey questions interrogated motivation, dietary intake patterns, symptoms suggestive of nutritional deficiencies or other adverse effects, satisfaction, prior and current health conditions, anthropometrics, and laboratory data.A total of 2029 respondents (median age: 44 y, 67% male) reported consuming a carnivore diet for 14 mo (IQR: 9–20 mo), motivated primarily by health reasons (93%). Red meat consumption was reported as daily or more often by 85%. Under 10% reported consuming vegetables, fruits, or grains more often than monthly, and 37% denied vitamin supplement use. Prevalence of adverse symptoms was low (<1% to 5.5%). Symptoms included gastrointestinal (3.1%–5.5%), muscular (0.3%–4.0%), and dermatologic (0.1%–1.9%). Participants reported high levels of satisfaction and improvements in overall health (95%), well-being (66%–91%), various medical conditions (48%–98%), and median [IQR] BMI (in kg/m2) (from 27.2 [23.5–31.9] to 24.3 [22.1–27.0]). Among a subset reporting current lipids, LDL-cholesterol was markedly elevated (172 mg/dL), whereas HDL-cholesterol (68 mg/dL) and triglycerides (68 mg/dL) were optimal. Participants with diabetes reported benefits including reductions in median [IQR] BMI (4.3 [1.4–7.2]), glycated hemoglobin (0.4% [0%–1.7%]), and diabetes medication use (84%–100%).Contrary to common expectations, adults consuming a carnivore diet experienced few adverse effects and instead reported health benefits and high satisfaction. Cardiovascular disease risk factors were variably affected. The generalizability of these findings and the long-term effects of this dietary pattern require further study.
Published:
December 1, 2021
Title:
Heart disease: The forgotten pandemic
Authors:
DuBroff, Robert; Demasi, Maryanne
Abstract:
Over the past 10 years cholesterol levels have been falling while the number of Americans dying of heart disease has been steadily climbing. This apparent paradox compels us to question whether lowering cholesterol is the best way to prevent coronary heart disease. A number of recent studies suggest that cholesterol, specifically LDL-C, may not be a primary risk factor for coronary heart disease and other markers, such as insulin resistance or remnant cholesterol, may be much more important. Furthermore, therapies designed to prevent coronary heart disease by lowering cholesterol with drugs or diet have yielded inconsistent results. Despite the widespread utilization of cholesterol-lowering statins in Europe, observational studies indicate that there has been no accompanying decline in coronary heart disease deaths. This new evidence should give us pause as we try to understand why the campaign to prevent heart disease by lowering cholesterol has not achieved its goals.
Published:
December 1, 2021
Title:
Intravenous ketogenic diet therapy for neonatal-onset pyruvate dehydrogenase complex deficiency
Authors:
Inui, Takehiko; Wada, Yoichi; Shibuya, Moriei; Arai-Ichinoi, Natsuko; Okubo, Yukimune; Endo, Wakaba; Uchida, Toshihiko; Togashi, Noriko; Naito, Etsuo; Haginoya, Kazuhiro
Abstract:
BACKGROUND: Pyruvate dehydrogenase complex (PDHC) deficiency is an inborn error of metabolism that causes lactic acidosis and neurodevelopmental changes. Five causative genes have been identified: PDHA1, PDHB, DLAT, DLD, and PDHX. Four neurological phenotypes have been reported: neonatal encephalopathy with lactic acidosis, non-progressive infantile encephalopathy, Leigh syndrome, and relapsing ataxia. Of these, neonatal encephalopathy has the worst mortality and morbidity and there is no effective treatment. SUBJECTS AND METHODS: We studied two girls who were clinically diagnosed with PDHC deficiency as neonates; they were subsequently found to have PDHA1 mutations. The clinical diagnosis was based on white matter loss and a lateral ventricular septum on fetal MRI, spasticity of the lower extremities, and lactic acidosis worsening after birth. Intravenous ketogenic diets were started within 24 h after birth. The ketogenic ratio was increased until the blood lactate level was controlled, while monitoring for side effects. RESULTS: In both cases, the lactic acidosis improved immediately with no apparent side effects. Both children had better developmental outcomes than previously reported cases; neither exhibited epilepsy. CONCLUSIONS: Intravenous ketogenic diet therapy is a treatment option for neonatal-onset PDHC deficiency. Further studies are needed to optimize this therapy.
Published:
December 1, 2021
Title:
Ketogenic Diet Impairment of Mycobacterium ulcerans Growth and Toxin Production and Enhancement of Host Response to Infection in an Experimental Mouse Model
Authors:
Foulon, Mélanie; Robbe-Saule, Marie; Esnault, Lucille; Malloci, Marine; Mery, Anthony; Saint-André, Jean-Paul; Croue, Anne; Kempf, Marie; Homedan, Chadi; Marion, Estelle; Marsollier, Laurent
Abstract:
Ketogenic diets have been used to treat diverse conditions, and there is growing evidence of their benefits for tissue repair and in inflammatory disease treatment. However, their role in infectious diseases has been little studied. Buruli ulcer (Mycobacterium ulcerans infection) is a chronic infectious disease characterized by large skin ulcerations caused by mycolactone, the major virulence factor of the bacillus. In the current study, we investigated the impact of ketogenic diet on this cutaneous disease in an experimental mouse model. This diet prevented ulceration, by modulating bacterial growth and host inflammatory response. β-hydroxybutyrate, the major ketone body produced during ketogenic diet and diffusing in tissues, impeded M. ulcerans growth and mycolactone production in vitro underlying its potential key role in infection. These results pave the way for the development of new patient management strategies involving shorter courses of treatment and improving wound healing, in line with the major objectives of the World Health Organization.
Published:
December 1, 2021
Title:
Subsistence behavior during the Initial Upper Paleolithic in Europe: Site use, dietary practice, and carnivore exploitation at Bacho Kiro Cave (Bulgaria)
Authors:
Smith, Geoff M.; Spasov, Rosen; Martisius, Naomi L.; Sinet-Mathiot, Virginie; Aldeias, Vera; Rezek, Zeljko; Ruebens, Karen; Pederzani, Sarah; McPherron, Shannon P.; Sirakova, Svoboda; Sirakov, Nikolay; Tsanova, Tsenka; Hublin, Jean-Jacques
Abstract:
The behavioral dynamics underlying the expansion of Homo sapiens into Europe remains a crucial topic in human evolution. Owing to poor bone preservation, past studies have strongly focused on the Initial Upper Paleolithic (IUP) stone tool record. Recent excavations and extensive radiocarbon dating at Bacho Kiro Cave (Bulgaria) pushed back the arrival of IUP H. sapiens into Europe to ca. 45,000 years ago. This site has exceptional bone preservation, and we present the study of 7431 faunal remains from across two IUP layers (I and J) and one Middle Paleolithic layer (K). We identified a shift in site use and occupation intensity through time, marked by increased find density and human modifications in Layer I. Alongside a decrease in carnivore presence and seasonality data demonstrating human presence in all seasons, this indicates a more frequent or prolonged occupation of the site by IUP groups. Contrarily, the dietary focus across the IUP and Middle Paleolithic layers is similar, centered on the exploitation of species from a range of habitats including Bos/Bison, Cervidae, Equidae, and Caprinae. While body parts of large herbivores were selectively transported into the site, the bear remains suggest that these animals died in the cave itself. A distinct aspect of the IUP occupation is an increase in carnivore remains with human modifications, including these cave bears but also smaller taxa (e.g., Canis lupus, Vulpes vulpes). This can be correlated with their exploitation for pendants, and potentially for skins and furs. At a broader scale, we identified similarities in subsistence behavior across IUP sites in Europe and western Asia. It appears that the first IUP occupations were less intense with find densities and human modifications increasing in succeeding IUP layers. Moreover, the exploitation of small game appears to be limited across IUP sites, while carnivore exploitation seems a recurrent strategy.
Published:
December 1, 2021
Title:
The impact of the transition from broad-spectrum hunting to sheep herding on human meat consumption: Multi-isotopic analyses of human bone collagen at Aşıklı Höyük, Turkey
Authors:
Itahashi, Yu; Stiner, Mary C.; Erdal, Omur Dilek; Duru, Güneş; Erdal, Yilmaz Selim; Miyake, Yutaka; Güral, Demet; Yoneda, Minoru; Özbaşaran, Mihriban
Abstract:
At Aşıklı Höyük, one of the earliest Pre-pottery Neolithic mound sites in Central Anatolia, a shift in animal utilization from broad-spectrum exploitation of diverse animal species to a concentration on managed caprines has been observed. Changes in the balance of meat to plant foods over the same time frame remain an open question. In this study, carbon and nitrogen isotopic analyses of bulk collagen and compound-specific nitrogen isotopic analysis of amino acids were undertaken for the human remains to elucidate the dietary impact of the hunting to herding transition over a span of about 1000 years. The results showed that animal protein consumption did not change very much as managed sheep became the main source of meat. The contribution of animal protein to the total human diet at Aşıklı Höyük is similar to comparison data on later Neolithic farmers in Anatolia measured in previous studies. The early development of ungulate management and the increasing focus on just a few prey species do not appear to have forced drastic changes in the extent human carnivory from the early Pre-pottery Neolithic to the early Pottery Neolithic. However, human individuals showed similar isotopic compositions within the same buildings at Aşıklı, suggesting variation in food consumption by household.
Published:
December 1, 2021
Title:
The use of tooth marks for new research into identifying and understanding the first domestic dogs in Palaeolithic populations
Authors:
Yravedra, José; Herranz-Rodrigo, Darío; Mendoza, Cecilia; Aragón-Poza, Pablo; Courtenay, Lloyd A.
Abstract:
The domestication of wolves is a topic of great interest. To date, the most accepted hypotheses associate this phenomenon to the end of the Upper Palaeolithic, while many propose an earlier date closer towards the Aurignacian. The latter proposal hinges on extensive research using palaeontological, morphometric, biomolecular-isotopic, genetic data and microwear contributing valuable information to the current debates. Nevertheless, few confront the theoretical reasoning behind this process, analysing the sociocultural implications that link humans with canids. Under this premise the current overview considers the motivation behind this process while proposing new lines of investigation that may help confront these questions across the indirect methods using new technologies applied study of tooth marks of the sites.
Published:
December 1, 2021
Title:
Trophic ecology of a Late Pleistocene early modern human from tropical Southeast Asia inferred from zinc isotopes
Authors:
Bourgon, Nicolas; Jaouen, Klervia; Bacon, Anne-Marie; Dufour, Elise; McCormack, Jeremy; Tran, N. -Han; Trost, Manuel; Fiorillo, Denis; Dunn, Tyler E.; Zanolli, Clément; Zachwieja, Alexandra; Duringer, Philippe; Ponche, Jean-Luc; Boesch, Quentin; Antoine, Pierre-Olivier; Westaway, Kira E.; Joannes-Boyau, Renaud; Suzzoni, Eric; Frangeul, Sébastien; Crozier, Françoise; Aubaile, Françoise; Patole-Edoumba, Elise; Luangkhoth, Thonglith; Souksavatdy, Viengkeo; Boualaphane, Souliphane; Sayavonkhamdy, Thongsa; Sichanthongtip, Phonephanh; Sihanam, Daovee; Demeter, Fabrice; Shackelford, Laura L.; Hublin, Jean-Jacques; Tütken, Thomas
Abstract:
Tam Pà Ling, a cave site in northeastern Laos, has yielded the earliest skeletal evidence of Homo sapiens in mainland Southeast Asia. The reliance of Pleistocene humans in rainforest settings on plant or animal resources is still largely unstudied, mainly due to poor collagen preservation in fossils from tropical environments precluding stable nitrogen isotope analysis, the classical trophic level proxy. However, isotopic ratios of zinc (Zn) in bioapatite constitute a promising proxy to infer trophic and dietary information from fossil vertebrates, even under adverse tropical taphonomic conditions. Here, we analyzed the zinc isotope composition (66Zn/64Zn expressed as δ66Zn value) in the enamel of two teeth of the Late Pleistocene (63–46 ka) H. sapiens individual (TPL1) from Tam Pà Ling, as well as 76 mammal teeth from the same site and the nearby Nam Lot cave. The human individual exhibits relatively low enamel δ66Zn values (+0.24‰) consistent with an omnivorous diet, suggesting a dietary reliance on both plant and animal matter. These findings offer direct evidence of the broad utilization of resources from tropical rainforests by one of the earliest known anatomically modern humans in Southeast Asia.
Published:
December 1, 2021
Title:
Trophic ecology of a Late Pleistocene early modern human from tropical Southeast Asia inferred from zinc isotopes
Authors:
Bourgon, Nicolas; Jaouen, Klervia; Bacon, Anne-Marie; Dufour, Elise; McCormack, Jeremy; Tran, N. -Han; Trost, Manuel; Fiorillo, Denis; Dunn, Tyler E.; Zanolli, Clément; Zachwieja, Alexandra; Duringer, Philippe; Ponche, Jean-Luc; Boesch, Quentin; Antoine, Pierre-Olivier; Westaway, Kira E.; Joannes-Boyau, Renaud; Suzzoni, Eric; Frangeul, Sébastien; Crozier, Françoise; Aubaile, Françoise; Patole-Edoumba, Elise; Luangkhoth, Thonglith; Souksavatdy, Viengkeo; Boualaphane, Souliphane; Sayavonkhamdy, Thongsa; Sichanthongtip, Phonephanh; Sihanam, Daovee; Demeter, Fabrice; Shackelford, Laura L.; Hublin, Jean-Jacques; Tütken, Thomas
Abstract:
Tam Pà Ling, a cave site in northeastern Laos, has yielded the earliest skeletal evidence of Homo sapiens in mainland Southeast Asia. The reliance of Pleistocene humans in rainforest settings on plant or animal resources is still largely unstudied, mainly due to poor collagen preservation in fossils from tropical environments precluding stable nitrogen isotope analysis, the classical trophic level proxy. However, isotopic ratios of zinc (Zn) in bioapatite constitute a promising proxy to infer trophic and dietary information from fossil vertebrates, even under adverse tropical taphonomic conditions. Here, we analyzed the zinc isotope composition (66Zn/64Zn expressed as δ66Zn value) in the enamel of two teeth of the Late Pleistocene (63–46 ka) H. sapiens individual (TPL1) from Tam Pà Ling, as well as 76 mammal teeth from the same site and the nearby Nam Lot cave. The human individual exhibits relatively low enamel δ66Zn values (+0.24‰) consistent with an omnivorous diet, suggesting a dietary reliance on both plant and animal matter. These findings offer direct evidence of the broad utilization of resources from tropical rainforests by one of the earliest known anatomically modern humans in Southeast Asia.
Published:
December 1, 2021
Title:
Elevated LDL-Cholesterol with a Carbohydrate-Restricted Diet: Evidence for a ‘Lean Mass Hyper-Responder’ Phenotype
Authors:
Norwitz, Nicholas G; Feldman, David; Soto-Mota, Adrian; Kalayjian, Tro; Ludwig, David S
Abstract:
People commencing a carbohydrate-restricted diet (CRD) experience markedly heterogenous responses in LDL-cholesterol (LDLc), ranging from extreme elevations to a reduction.To elucidate possible sources of heterogeneity in LDLc response to a CRD and, thereby, identify individuals who may be at risk for LDLc elevation.Hypothesis-naive analyses were conducted on web survey data from 597 adults consuming a CRD. Univariate and multivariate regression models and regression trees were built to evaluate the interaction between BMI and baseline lipid markers. Data were also collected from a case series of five clinical patients with extremely high LDLc consuming a CRD.BMI was inversely associated with LDLc change. Low TG/HDLc ratio, a marker of good metabolic health, predicted larger LDLc increases. A sub-group of respondents with LDLc ≥200 mg/dL, HDLc ≥80 mg/dL, and TG ≤70 mg/dL were characterized as “Lean Mass Hyper-Responders.” Respondents with this phenotype (n = 112) had lower BMI and, remarkably, similar prior LDLc versus other respondents. In the case series, moderate reintroduction of carbohydrate produced a marked decrease in LDLc.These data suggest that, in contrast to the typical pattern of dyslipidemia, greater LDLc elevation on a CRD tends to occur in the context of low cardiometabolic risk.
Published:
November 30, 2021
Title:
酮体β-羟基丁酸减轻炎症状态下血管内皮细胞线粒体氧化应激的机制研究
Authors:
戢力维; 邓艳; 李涛
Abstract:
目的 探讨酮体β-羟基丁酸（β-OHB）对炎症状态下人脐静脉血管内皮细胞（HUVECs）线粒体氧化应激的调控作用及机制。 方法 用脂多糖（LPS）和三磷酸腺苷（ATP）诱导巨噬细胞释放促炎因子，收集培养基上清液作为条件培养基（macrophage-conditioned medium, MCM）培养HUVECs。研究共设置7组HUVECs细胞。①对照组：正常培养的HUVECs；②MCM组：MCM培养的HUVECs；③～⑦组为加入不同试剂的HUVECs共培养组，包括：③MCM+β-OHB组，④MCM+N-乙酰半胱氨酸（NAC）组，⑤MCM+β-OHB+NAC组，⑥MCM+β-OHB+组蛋白去乙酰化酶激动剂ITSA1组，⑦MCM+β-OHB+组蛋白去乙酰化酶抑制剂Entinostat组。MitoSOX免疫荧光染色分析线粒体超氧化物水平，实时荧光定量聚合酶链式反应（RT-qPCR）检测抗氧化基因mRNA表达，并以Seahorse线粒体能量分析仪测定线粒体有氧呼吸能力。 结果 与对照组相比，MCM培养的HUVECs细胞线粒体超氧化物生成明显增多，而β-OHB处理可明显抑制线粒体超氧化物生成，并伴随抗氧化基因mRNA表达水平上升，以及线粒体基础耗氧率和呼吸储备能力的显著提高。NAC处理并未进一步提高β-OHB对线粒体功能的保护作用。并且，ITSA1处理可完全取消β-OHB的抗氧化和线粒体保护作用，而Entinostat处理后上述作用仍然维持。 结论 酮体β-OHB通过抑制组蛋白去乙酰化酶活性，激活抗氧化通路，减轻血管内皮细胞的线粒体氧化应激。
Published:
November 29, 2021
Title:
Animal protein intake is inversely associated with mortality in older adults: the InCHIANTI study
Authors:
Meroño, Tomás; Zamora-Ros, Raúl; Hidalgo-Liberona, Nicole; Rabassa, Montserrat; Bandinelli, Stefania; Ferrucci, Luigi; Fedecostante, Massimiliano; Cherubini, Antonio; Andres-Lacueva, Cristina
Abstract:
In general, plant protein intake was inversely associated with mortality in studies in middle-aged adults. Our aim was to evaluate the long-term associations of animal and plant protein intake with mortality in older adults.A prospective cohort study including 1,139 community-dwelling older adults (mean age 75 years, 56% women) living in Tuscany, Italy, followed for 20 years (InCHIANTI study) was analyzed. Dietary intake by food frequency questionnaires and clinical information were assessed five times during the follow-up. Protein intakes were expressed as percentages of total energy. Time-dependent Cox regression models adjusted for confounders were used to assess the association between plant and animal protein intake, and mortality.During the 20-years of follow up (mean: 12y), 811 deaths occurred (292 of cardiovascular- and 151 of cancer-related causes). Animal protein intake was inversely associated with all-cause (HR per 1% of total energy from protein increase, 95%CI: 0.96, 0.93-0.99) and cardiovascular mortality (HR per 1% of total energy from protein increase, 95%CI: 0.93, 0.87-0.98). Plant protein intake showed no association with any of the mortality outcomes, but an interaction with baseline hypertension was found for all-cause and cardiovascular mortality (p<0.05).Animal protein was inversely associated with all-cause and cardiovascular mortality in older adults. Further studies are needed to provide recommendations on dietary protein intake for older adults.
Published:
November 27, 2021
Title:
Evaluation of the seizure control and the tolerability of ketogenic diet in Chinese children with structural drug-resistant epilepsy
Authors:
Dou, Xiangjun; Xu, Xiaoke; Mo, Tingting; Chen, Hua; Wang, Zhijing; Li, Xia; Jia, Shanshan; Wang, Dong
Abstract:
OBJECTIVES: In this study, we aimed to evaluate the efficacy and tolerability of ketogenic diet (KD) in Chinese children with drug-resistant epilepsy (DRE) due to structural etiology. METHODS: We retrospectively analyzed data from 23 pediatric patients with DRE due to structural etiology who were treated with KD at Department of Neurology, between May 2014 and December 2020. Based on etiological classifications, the patients were divided into a neonatal brain injury (Group 1), an intracranial infection group (Group2) and a group that showed malformations of cortical development (MCDs) (Group 3). RESULTS: The 23 patients remained on the KD for a mean duration of 15.3 ± 9.7 months. The response rates for the control of seizures were 60.9% (14/23), 52.2 % (12/23), 47.8% (11/23) at 3, 6 and 12 months, respectively. Subjective improvements in cognition were observed in 87.0% (20/23) of the children during follow-up. Reductions in the frequency of seizures of > 50% were more commonly achieved by patients in group 1 (75.0%, 9/12) compared to the patients in groups 2 (60.0%, 3/5) and 3 (33.4%, 2/6). Further analysis of the patients in Group 1 showed that children with a history of hypoxic ischemic encephalopathy (HIE) (100.0%, 6/6) had the highest rate of > 50% seizure reduction. The main reasons for the discontinuation of the KD were due to lack of efficacy and poor compliance. Most of the side effects associated with the KD diet were minor and easily corrected by appropriately adjusting the diet. Only 1 patient discontinued the diet due to severe refusal to eat. CONCLUSIONS: KD is an effective and safe treatment for Chinese children with DRE due to structural etiology. Better efficacy of seizure control was observed in patients with a history of neonatal brain injury. Patients with DRE secondary to HIE may be particularly responsive to the KD therapy, and so KD should be considered earlier in those patients.
Published:
November 25, 2021
Title:
Can older patients adopt and maintain a ketogenic diet? An observational study in support of clinical trials in older patients
Authors:
Almodallal, Yahya; Cook, Kathryn; Lammert, Lisa M.; Lee, Minji; Le-Rademacher, Jennifer G.; Jatoi, Aminah
Abstract:
Ketogenic diets appear promising for obesity, diabetes, cancer, and other illnesses. Because older patients are more likely to contend with such illnesses and because of a paucity of dietary outcomes among these patients, we examined ketogenic diets in older patients. This multisite study focused on patients (≥65 years of age) on a ketogenic diet. Medical records were identified with the keywords “keto,” “ketogenic,” and “Atkins.” Records were reviewed in detail with extraction of direct quotations to substantiate observations. We report on 200 consecutive patients with a median age of 70 years. Reasons for diet included weight loss, diabetes, and cancer; the majority remained on the diet for >1 month. In 134 (67%: 95% confidence interval: 60, 73%), the ketogenic diet appeared beneficial: 93 of 117 (79%) who sought weight loss lost weight (“She has lost 15 pounds and plans to lose another 8”); 36 of 67 (54%) who sought glucose control appeared to achieve the latter (“He has gone on a ketogenic diet and has been able to bring his sugars down significantly”); and 5 of 8 (63%) who sought improved cancer outcomes appeared to derive them (“He attributes part of the control of his cancer and increased QOL to adopting the keto for cancer diet”). Adverse events occurred in 30 patients (15%): dyslipidemia (n = 14), constipation (n = 9), sub-therapeutic international normalized ratio (n = 3), pancreatitis (n = 2), diarrhea (n = 1), and fatigue (n = 1). Trials that test ketogenic diets for a variety of illnesses should enroll older adults.
Published:
November 24, 2021
Title:
Novel UBE3A pathogenic variant in a large Georgian family produces non-convulsive status epilepticus responsive to ketogenic diet
Authors:
Melikishvili, Gia; Bienvenu, Thierry; Tabatadze, Nazhi; Gachechiladze, Tamar; Kurua, Ekaterine; Gverdtsiteli, Sopio; Melikishvili, Mariam; Dulac, Olivier
Abstract:
PURPOSE: To report the effect of the ketogenic diet (KD) on non-convulsive status epilepticus (NCSE) due to Angelman syndrome (AS) in two members of a large Georgian family affected by a novel frameshift variant in the UBE3A gene (NM_000462.3). METHODS: We evaluated two members of this family who were affected with clinical and EEG features of AS. Clinical history with special emphasis on development, seizure type, frequency, and treatment was reviewed. Routine and long-term video EEG monitoring were conducted, particularly during NCSE. A non-fasting inpatient KD protocol was implemented using blended food orally with full administration of 4:1 (fat to non-fat) ratio. Urine ketone bodies (KBs), measured with urine ketone acetone strips readings, reached 150 mg/dL in both patients. RESULTS: Patients had characteristic signs of AS and presented with epilepsy between the age of 2-4 years. As methylation tests were negative, next generation sequencing disclosed a c.2365del variant. For both, NCSE was revealed by cognitive deterioration and did not respond to anti-seizure medication. As recommended, IV pyridoxine, benzodiazepines, and valproic acid were administered, but without success. For both patients, NCSE resolved on the second-third day of KD initiation, before the appearance of ketonuria and resulting in improved communication, mood and sleep. CONCLUSION: KD is safe and effective for the treatment of NCSE due to AS. Resolution before the appearance of ketone bodies points to a possible mechanism of action of KD.
Published:
November 24, 2021
Title:
Trends in Obesity Prevalence Among Adults Aged 18 Through 25 Years, 1976-2018
Authors:
Ellison-Barnes, Alejandra; Johnson, Sara; Gudzune, Kimberly
Abstract:
Emerging adulthood, from ages 18 through 25 years, is a distinct developmental period characterized by exploration and frequent change (eg, from school to work), ultimately leading to the formation of lifelong habits and adult identity. Few studies describe obesity in emerging adults; analyses often group these individuals with adolescents (aged 12-19 years) or young adults (aged 20-39 years), limiting opportunities for developmentally informed intervention and treatment. We examined the changes in obesity prevalence nationally among emerging adults in the US over the last 4 decades.
Published:
November 23, 2021
Title:
Does Linoleic Acid Induce Obesity? A Response to Stephan Guyenet. Part 2
Authors:
Abstract:
Published:
November 18, 2021
Title:
Behavioral Characteristics and Self-reported Health Status Among 2029 Adults Consuming a “Carnivore Diet”
Authors:
Lennerz, Belinda S; Mey, Jacob T; Henn, Owen H; Ludwig, David S
Abstract:
The “carnivore diet,” based on animal foods and excluding most or all plant foods, has attracted recent popular attention. However, little is known about the health effects and tolerability of this diet, and concerns for nutrient deficiencies and cardiovascular disease risk have been raised.We obtained descriptive data on the nutritional practices and health status of a large group of carnivore diet consumers.A social media survey was conducted March 30 to June 24, 2020 among adults self- identifying as consuming a carnivore diet ≥ 6 months. Survey questions interrogated motivation, dietary intake patterns, symptoms suggestive of nutritional deficiencies or other adverse effects, satisfaction, prior and current health conditions, anthropometrics, and laboratory data.A total of 2029 respondents (median age 44 years, 67% male), reported consuming a carnivore diet for 14 (interquartile range 9–20) months, motivated primarily by health reasons (93%). Red meat consumption was reported ≥ daily by 85%. Under 10% reported consuming vegetables, fruits or grains > monthly, and 37% denied vitamin supplement use. Prevalence of adverse symptoms was low (<1% to 5.5%). Symptoms included gastrointestinal (3.1–5.5%), muscular (4.0%), and dermatologic (1.1–1.9%). Participants reported high levels of satisfaction and improvements in overall health (95%), wellbeing (69–91%), various medical conditions (48–93%) and BMI (from 27.2 [23.5–31.9] to 24.3 [22.1–27.0] kg/m2). Among a subset reporting current lipids, LDL-cholesterol was markedly elevated (172 mg/dL), whereas HDL-cholesterol (68 gm/dL) and triglycerides (68 mg/dL) were optimal. Participants with diabetes reported benefits including reductions in BMI (4.3 kg/m2, 1.4–7.2), HbA1C (0.4%, 0–1.7), and diabetes medication use (84–100%).Contrary to common expectations, adults consuming a carnivore diet experienced few adverse effects and instead reported health benefits and high satisfaction. Cardiovascular risk factors were variably affected. The generalizability of these findings and the long-term effects of this dietary pattern require further study.In a survey of over 2000 adults following a “carnivore diet” (i.e., one that aims to avoid plant foods), health benefits and satisfaction were generally reported.
Published:
November 2, 2021
Title:
Neural mechanisms that promote food consumption following sleep loss and social stress: An fMRI study in adolescent girls with overweight/obesity
Authors:
Jensen, Chad D.; Zaugg, Kelsey K.; Muncy, Nathan M.; Allen, Whitney D.; Blackburn, Robyn; Duraccio, Kara M.; Barnett, Kimberly A.; Kirwan, C. Brock; Jarcho, Johanna M.
Abstract:
STUDY OBJECTIVES: Insufficient sleep and social stress are associated with weight gain and obesity development in adolescent girls. Functional magnetic resonance imaging (fMRI) research suggests that altered engagement of emotion-related neural networks may explain overeating when under stress. The purpose of this study is to explore the effects of acute sleep restriction on female adolescents' neural responding during social evaluative stress and their subsequent eating behavior. METHODS: Forty-two adolescent females (ages 15-18 years) with overweight or obesity completed a social stress induction task in which they were told they would be rated by peers based on their photograph and profile. Participants were randomly assigned to one night of sleep deprivation or 9 hours of sleep the night before undergoing fMRI while receiving positive and negative evaluations from their peers. After which, subjects participated in an ad libitum buffet. RESULTS: Sleep deprived, relative to non-deprived girls had distinct patterns of neural engagement to positive and negative evaluation in anterior, mid, and posterior aspects of midline brain structures. Moreover, a sleep deprivation-by-evaluation valence-by-caloric intake interaction emerged in bilateral dorsal anterior cingulate. Among sleep deprived girls, greater engagement during negative, but not positive, feedback was associated with lower caloric intake. This was not observed for non-sleep deprived girls. CONCLUSIONS: Results suggest an interaction between acute sleep loss and social evaluation that predicts emotion-related neural activation and caloric intake in adolescents. This research helps to elucidate the relationship between sleep loss, social stress, and weight status using a novel health neuroscience model.
Published:
November 2, 2021
Title:
Brief Literature Review: Glycemic Control With Ketogenic Diet in People With Diabetes
Authors:
Gordon, Peter Martin; Clements, Jennifer N.
Abstract:
Evidence does not support a clear preference for a specific eating pattern for people with diabetes, yet recommendations should be evidence-based, standardized, and individualized. Current nutrition guidelines focus on whole foods and dietary patterns rather than specific nutrients (1). The ketogenic eating pattern was initially used as adjunctive therapy for epilepsy (2). However, recent evidence suggests that a ketogenic eating pattern may improve glycemic control in people with type 2 diabetes (2). The macronutrient intake of people on a ketogenic diet predominantly consists of 55–60% fat, 30–35% protein, and
Published:
November 1, 2021
Title:
Early Upper Paleolithic subsistence in the Levant: Zooarchaeology of the Ahmarian–Aurignacian sequence at Manot Cave, Israel
Authors:
Yeshurun, Reuven; Schneller-Pels, Nehora; Barzilai, Omry; Marder, Ofer
Abstract:
The Early Upper Paleolithic period in the Levant is essential in the studies of the establishment of modern human communities outside Africa, and corresponding archaeological evidence may be used to shed light on human ecology, economy and demography. Specifically, cultural differences between two Early Upper Paleolithic entities, the Early Ahmarian and the Levantine Aurignacian, raise the question of differing adaptations. In this article we use archaeofaunal remains from the Early Upper Paleolithic sequence at Manot Cave (Western Galilee, Israel), to track human hunting patterns, carcass transport and processing within the Early Ahmarian (46–42 ka) and Levantine Aurignacian (38–34 ka) phases. We test two hypotheses: 1) the Ahmarian and Aurignacian represent adaptations to different environments; and 2) the two entities differ in mobility patterns and site use. Our multivariate taphonomic analysis showed subtle differences in depositional processes between the two phases and demonstrated a primarily anthropogenic complex. In both phases, human subsistence was based on two ungulate species, mountain gazelle (Gazella gazella) and Mesopotamian fallow deer (Dama mesopotamica), with some contribution from birds, tortoises and small mammals. Among the gazelles, it appears that female herds were targeted, and that hunting took place close to the cave. The results of the research show great similarity in environmental exploitation between the Ahmarian and Aurignacian phases concerning prey spectrum and choice, carcass transport and processing. These patterns occupy a middle position between the Middle Paleolithic and the late Epipaleolithic of the region. Despite this, there are also several significant differences between the phases such as increased exploitation of small game (especially birds) and faster accumulation and higher densities of material in the Aurignacian. This may indicate greater occupation intensity during the Aurignacian compared to the Ahmarian, and thus could explain the outstanding character of this entity in the Levant.
Published:
November 1, 2021
Title:
Hypothesis on Pollution of Neuronal Membranes, Epilepsy and Ketogenic Diet
Authors:
Nechipurenko, Yu. D.; Reyes, R. C. Garcia; Caceres, J. L. Hernandez
Abstract:
Taking into account recent facts, Altrup’s neuron’s membrane pollution hypothesis for epilepsy is dealt with. This hypothesis links paroxysmal depolarization shifts observed during epileptic activity, and single-neuron pacemaker potentials. Membrane’s physicochemical characteristics, fluidity and pollution influence on its capability to conduct impulses and polarize. Previously used means of epilepsy treatment based on the ketogenic diet, as well as their possible mechanisms are discussed on the light of Altrup’s hypothesis. Among possible action mechanisms for ketogenic diet, we underline ketone bodies antiepileptic action, the role of increased synthesis of glutathione and the effect of polyunsaturated fatty acids (PUFA) and cholesterol as components included into the ketogenic diet. These three mechanisms, among others, lead to a regulation of fluidity and other biophysical properties of the membrane bilayer as well as to a cleansing of the membrane from amphiphilic polluters, in accordance with Altrup’s hypothesis.
Published:
November 1, 2021
Title:
Vegetarian diet and depression scores: A meta-analysis
Authors:
Ocklenburg, Sebastian; Borawski, Jette
Abstract:
Background Several studies have suggested an association between vegetarian diet and higher depression scores. However, some studies have also shown an effect in the opposite direction, indicating lower depression scores in vegetarians. Given this discrepancy in the literature, this meta-analysis was aimed to determine whether there is a significant association between vegetarian diet and depression scores across different published studies. Methods A keyword search in major databases was conducted. Studies reporting depression scores in vegetarians and a non-vegetarian control group were included. Meta-analysis following a conditional random-effects procedure was conducted in R. Results After duplicates were removed and studies were analyzed for inclusion criteria, k=13 studies with an overall n of 49889 participants (8057 vegetarians and 41832 non-vegetarian controls) were included in the analysis. Random-effects meta-analysis revealed a significant difference between vegetarians and non-vegetarians, with vegetarians showing higher depression scores than non-vegetarians. Limitations The heterogeneity between studies was high and geographical variation in study location was low, limiting cross-cultural insights. Conclusions Vegetarians show higher depression scores than non-vegetarians. However, due to high heterogeneity of published studies, more empirical research is needed before any final conclusions can be drawn. Also, empirical studies from a higher number of different countries would be desirable.
Published:
November 1, 2021
Title:
Influence of Ketogenic Diet and Nutraceutical Correction in the Complex Treatment of Lower Limbs Lipedema
Authors:
Apkhanova, Tatyana V.; Sergeev, Valery N.; Krukova, Marina M.; Vasilyeva, Valeria A.; Kulchitskaya, Detelina B.; Konchugova, Tatyana V.; Sapelkin, Sergey V.
Abstract:
Currently, the ketogenic diet (KD) is used to treat obesity. A prospective study on the use of KD and nutraceutical correction of the nutritional status of patients with lipedema was carried out. Aim. To study the effect of the ketogenic diet, accompanied by correction of changes in the intestinal microbiome and hepatoprotection,on the reduction of fatty deposits in lipedema and the dynamics of changes in lipid and carbohydrate metabolism hormones. Material and methods. 60 patients with lower limb lipedema of stages I-III were randomized into 2 groups: Group 1 received a lowcalorie diet (LCD), physical exercises in the gym (PE), and physical activity (FA) in the form of daily walking up to 3-5 km/ day. Group 2 received a modified version of the Atkins ketogenic diet, physical exercises in the gym and FA, as well as nutraceutical correction of increased appetite, probiotic intestinal composition, hepatoprotection. The duration of the treatment course was 4 weeks. Anthropometric methods and bioimpedansometry were used to control limb circumferences, waist and thigh. Results and discussion. After treatment, patients in 1st group showed a decrease in body weight, lean and active cell mass, a decrease in musculoskeletal mass, and a decrease in total water due to extracellular water. A decrease in total cholesterol and high density lipoproteins (HDL) fraction, an increase in blood triglyceride fraction was noted. Leptin decreased by 12.73%. Patients of the 2nd group showed a decrease in body weight, fat mass, lean mass, total water and extracellular water. There was a decrease in total cholesterol, triglycerides, transaminases. Leptin decreased by 32.02%, insulin decreased by 9.87%. To prevent the development of fatty hepatosis against the background of the use of KD, patients of the 2nd group received nutraceutical correction: hepatoprotector Gepamin, metaprebiotic Stimbifid-plus, modulating the formation of resident intestinal microbiota. To reduce appetite, the patients of the 2nd group were also prescribed anorexic - an algal product Nativ containing the polysaccharide fucoidan, having a prebiotic effect. Improvement of reparative processes in the liver, suppression of oxidative processes also contributed to the restoration of the sensitivity of insulin receptors, which was confirmed by the normalization of the lipid-carbohydrate spectrum of blood in patients of the 2nd group after the course of the treatment. The insulin decrease in patients of Group 2 indicated not only insulin resistance decrease , but also the lipogenesis decrease and stimulation of lipolysis. Adipose tissue reduction due to lipolysis stimulation was also indicated by a decrease in leptin expression. Conclusion. Thus, a ketogenic diet, accompanied by nutraceutical correction of the intestinal microbiome and hepatoprotection can be effectively used in combination with physical activity in order to reduce body weight, fat mass and edema, as evidenced by a decrease in the expression level of leptin and insulin, correlating with the levels of fat loss and free water.
Published:
October 31, 2021
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