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Introduction: Contamination of cocoa containing products, such as dark chocolate, with heavy metals including lead, cadmium and arsenic has been reported in the US. However, a formal exploration into the significance of this contamination, nor multi-year trends in the degree or scope remain unresolved. Methods: From 2014 to 2022, 72 consumer cocoa-containing products were purchased and analyzed for heavy metal contamination with lead (Pb), cadmium (Cd), and arsenic (As) in 4 distinct cohorts (2014, 2016, 2019, 2022). The thresholds used to assess heavy metal contamination were set to Prop 65 maximum allowable dose levels (MADLs) of 0.5 mcg/day, 4.1 mcg/day, 10 mcg/day for Pb, Cd, and As, respectively. Results and discussion: Our analysis reports that 43, 35, and 0% of the products tested exceed Prop 65 MADLs for heavy metal concentrations, respectively, of Pb, Cd, and As, while 97.2% (70 of 72) fall below US FDA IRL limits established for Pb. Median concentrations of each metal tested were lower than even the conservative Prop 65 MADLs, indicating a potentially large effect of product outliers. This indicates that heavy metal contamination-in more than half of products tested-may not pose any appreciable risk for the average person when consumed as a single serving; however, consuming some of the products tested, or more than one serving per day in combination with non-cocoa derived sources heavy metals, may add up to exposure that would exceed the Prop 65 MADLs. Notably, "organic" products were significantly more likely to demonstrate higher levels of both Cd and Pb.
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Importance: Research is beginning to elucidate the sophisticated mechanisms underlying the microbiota-gut-brain-immune interface, moving from primarily animal models to human studies. Findings support the dynamic relationships between the gut microbiota as an ecosystem (microbiome) within an ecosystem (host) and its intersection with the host immune and nervous systems. Adding this to the effects on epigenetic regulation of gene expression further complicates and strengthens the response. At the heart is inflammation, which manifests in a variety of pathologies including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Multiple Sclerosis (MS). Observations: Generally, the research to date is limited and has focused on bacteria, likely due to the simplicity and cost-effectiveness of 16s rRNA sequencing, despite its lower resolution and inability to determine functional ability/alterations. However, this omits all other microbiota including fungi, viruses, and phages, which are emerging as key members of the human microbiome. Much of the research has been done in pre-clinical models and/or in small human studies in more developed parts of the world. The relationships observed are promising but cannot be considered reliable or generalizable at this time. Specifically, causal relationships cannot be determined currently. More research has been done in Alzheimer's disease, followed by Parkinson's disease, and then little in MS. The data for MS is encouraging despite this. Conclusions and relevance: While the research is still nascent, the microbiota-gut-brain-immune interface may be a missing link, which has hampered our progress on understanding, let alone preventing, managing, or putting into remission neurodegenerative diseases. Relationships must first be established in humans, as animal models have been shown to poorly translate to complex human physiology and environments, especially when investigating the human gut microbiome and its relationships where animal models are often overly simplistic. Only then can robust research be conducted in humans and using mechanistic model systems.
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Eje Cerebro-Intestino , Encéfalo , Microbioma Gastrointestinal , Enfermedades Neuroinflamatorias , Humanos , Microbioma Gastrointestinal/inmunología , Animales , Eje Cerebro-Intestino/inmunología , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/microbiología , Enfermedades Neuroinflamatorias/etiología , Encéfalo/inmunología , Encéfalo/microbiologíaRESUMEN
More than 20% of American adults live with a mental disorder, many of whom are treatment resistant or continue to experience symptoms. Other approaches are needed to improve mental health care, including prevention. The role of the microbiome has emerged as a central tenet in mental and physical health and their interconnectedness (well-being). Under normal conditions, a healthy microbiome promotes homeostasis within the host by maintaining intestinal and brain barrier integrity, thereby facilitating host well-being. Owing to the multidirectional crosstalk between the microbiome and neuro-endocrine-immune systems, dysbiosis within the microbiome is a main driver of immune-mediated systemic and neural inflammation that can promote disease progression and is detrimental to well-being broadly and mental health in particular. In predisposed individuals, immune dysregulation can shift to autoimmunity, especially in the presence of physical or psychological triggers. The chronic stress response involves the immune system, which is intimately involved with the gut microbiome, particularly in the process of immune education. This interconnection forms the microbiota-gut-immune-brain axis and promotes mental health or disorders. In this brief review, we aim to highlight the relationships between stress, mental health, and the gut microbiome, along with the ways in which dysbiosis and a dysregulated immune system can shift to an autoimmune response with concomitant neuropsychological consequences in the context of the microbiota-gut-immune-brain axis. Finally, we aim to review evidenced-based prevention strategies and potential therapeutic targets.
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Eje Cerebro-Intestino , Encéfalo , Disbiosis , Microbioma Gastrointestinal , Trastornos Mentales , Salud Mental , Estrés Psicológico , Humanos , Microbioma Gastrointestinal/inmunología , Eje Cerebro-Intestino/inmunología , Estrés Psicológico/inmunología , Estrés Psicológico/microbiología , Disbiosis/inmunología , Trastornos Mentales/inmunología , Trastornos Mentales/microbiología , Encéfalo/inmunología , Animales , NeuroinmunomodulaciónRESUMEN
Background: A multidisciplinary team of health scientists and educators at an academic medical center came together to consider the various factors that impact well-being among self-identified women working in healthcare and conducted a comprehensive literature review to identify the existing body of knowledge. Objectives: To examine how well-being is defined, what instruments are used to measure it, and correlation between professional and personal gender-specific factors that impact the well-being of women in healthcare occupations. Methods: A total of 71 studies published in 26 countries between 1979-2022 were extracted from PubMed. Studies enrolled adult women (18-74 y.o.) healthcare professionals including nurses, physicians, clinical social workers, and mental health providers. Well-being related phenomena such as quality of life (QOL), stress, burnout, resiliency, and wellness were investigated. In this review, women are broadly defined to include any individual who primarily identifies as a woman regardless of their sex assigned at birth. Results: The results of our analysis were consistent across the scope of the literature and indicated that women in healthcare occupations endure a significantly higher level of stress and burnout compared to their male counterparts. The following gender-specific factors were identified as having direct correlation to well-being: job satisfaction, psychological health, and work-life integration. Conclusions: The findings from this review indicate a need for evidence-based integrative interventions across healthcare enterprises to combat stress and burnout and strengthen the resiliency and well-being of women in healthcare. Using information from this review, our team will launch a comprehensive well-being assessment and a series of interventions to support resiliency and well-being at our academic medical center.
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Background: A pro-inflammatory metabolic state is key to the chronic disease epidemic. Clinicians' ability to use nutrients to balance inflammation via oxidant homeostasis depends on the quality of antioxidants research. Understanding the intersection of two prominent theories for how antioxidants quell inflammation-nutritional hormesis and oxidant scavenging-will enable therapeutic antioxidant use in clinical practice. Purpose: We sought to survey the literature to answer the question: has the hormetic response of exogenous antioxidants been studied in humans and if so, what is its effect Research Design: This review investigates the less well-established theory, nutritional hormesis. To understand the state of hormetic response research, we conducted a literature review describing the relationship between exogenous antioxidants, hormesis, and chronic disease. We used an adaptive search strategy (PubMed and Scopus), retrieving 343 articles, of which 218 were unique. Most studies reviewed the hormetic response in plant and cell models (73.6%) while only 2.2% were in humans. Results: Given the limited robust evidence, clinicians lack research-based guidance on the appropriate therapeutic dose of exogenous antioxidants or, more concerning, supra-physiological dosing via supplements. A critical hurdle in searching the literature is the lack of standardized nomenclature describing the hormetic effect, challenging the ability of clinicians to make informed decisions. Conclusion: Non-human research shows a biphasic, hormetic relationship with antioxidants but observational studies have yet to translate this into the complexities of human biochemistry and physiology. Therefore, we cannot accurately translate this into clinical care. To remedy this insufficiency, we suggest: (1) Improved data collection quality: controlled diet, standardized antioxidant measurements, bioavailability assessed via biomarkers; (2) Larger, harmonized datasets: research subject transparency, keyword standardization, consensus on a hormesis definition.
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There exists significant heterogeneity in the 'freshness' of consumer marine- and plant-derived omega-3 (Ω3) supplements. Fears of rancidity, or the oxidation of consumer Ω3 supplements, has been debated in the literature with several prior authors reporting contradictory findings. We report the peroxide value (PV), para-anisidine value (p-AV) and total oxidation values (TOTOX) associated with 72 consumer Ω3 supplements sold in the United States sampled from 2014-2020. The effect of flavoring on the oxidation of the supplements was examined in an adjusted fixed effects model controlling for type of delivery system (enteric, liquid, animal- and vegetable-derived gelatin softgel, spray), source (algae, calamari, fish, krill, mussels), and certifications assigned by third-party organizations (e.g. USP). Overall, our results revealed that 68% (23/34) of flavored and 13% (5/38) unflavored consumer Ω3 supplements exceeded the TOTOX upper limit set by the Global Organization for EPA and DHA (GOED) voluntary monograph standard of ≤ 26, with 65% (22/34) flavored supplements and 32% (12/38) unflavored supplements failing the PV upper limit of ≤ 5 and 62% (21/34) flavored supplements exceeding the p-AV upper limit of ≤ 20. To our knowledge, no prior authors have modeled the impact of flavoring on oxidative status in 72 marine- and plant-derived Ω3 products sold in the U.S. We present our findings in this context and discuss the clinical implications related to the consumption of oxidized consumer fish oils and their effects on human health.
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Ácidos Grasos Omega-3 , Animales , Humanos , Suplementos Dietéticos/análisis , Aceites de Pescado/análisis , Oxidación-Reducción , Compuestos de AnilinaRESUMEN
In this review, we explore the potential drivers of heterogeneity in response to Vitamin D (VitD) therapy, such as bioavailability, sex-specific response, and autoimmune pathology, in those at risk for and diagnosed with T2DM. In addition, we propose distinct populations for future interventions with VitD. The literature concerning VitD supplementation in the prevention, treatment, and remission of type 2 diabetes mellitus (T2DM) spans decades, is complex, and is often contradictory with mixed findings upon intervention. By association, VitD status is powerfully predictive with deficient subjects reporting greater risk for T2DM, conversion to T2DM from prediabetes, and enhanced response to VitD therapy. Preclinical models strongly favor intervention with VitD owing to the pleiotropic influence of VitD on multiple systems. Additional research is crucial as there remain many questions unanswered that are related to VitD status and conditions such as T2DM. Future research must be conducted to better understand the potentially spurious relationships between VitD status, supplementation, sun exposure, health behaviors, and the diagnosis and management of T2DM. Public health practice can greatly benefit from a better understanding of the mechanisms by which we can reliably increase VitD status and how this can be used to develop education and improve health behaviors.
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Diabetes Mellitus Tipo 2 , Deficiencia de Vitamina D , Masculino , Femenino , Humanos , Vitamina D/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Vitaminas/uso terapéutico , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/complicaciones , Suplementos DietéticosRESUMEN
Nutrition is a foundation of health and one of six pillars of Lifestyle Medicine. The importance of nutrition in clinical care is now widely recognized by health care professionals and the public. However, clinicians are not comfortable counselling their patients on nutrition due to inadequate or lack of training, leaving a significant need in patient care. This gap can be closed with evidence-based curricula in medical schools and in the trainings of other health care professionals. This communication presents the current state of nutrition knowledge in health care, emphasizing nutrition education for physicians, and presents a model of how pre- through post-professional health care providers may become proficient in nutrition counseling including appropriate referral to more specialized providers. With these skills, health care professionals will be able to initiate patient-centered lifestyle plans. This includes improving diet and utilization of team-based medicine and referrals.
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Medicina , Médicos , Curriculum , Humanos , Estilo de Vida , Facultades de MedicinaRESUMEN
CONTEXT: The ability to measure the gut microbiome led to a surge in understanding and knowledge of its role in health and disease. The diet is a source of fuel for and influencer of composition of the microbiome. OBJECTIVE: To assess the understanding of the interactions between nutrition and the gut microbiome in healthy adults. DATA SOURCES: PubMed and Google Scholar searches were conducted in March and August 2018 and were limited to the following: English, 2010-2018, healthy adults, and reviews. DATA EXTRACTION: A total of 86 articles were independently screened for duplicates and relevance, based on preidentified inclusion criteria. DATA ANALYSIS: Research has focused on dietary fiber - microbiota fuel. The benefits of fiber center on short-chain fatty acids, which are required by colonocytes, improve absorption, and reduce intestinal transit time. Contrastingly, protein promotes microbial protein metabolism and potentially harmful by-products that can stagnate in the gut. The microbiota utilize and produce micronutrients; the bidirectional relationship between micronutrition and the gut microbiome is emerging. CONCLUSIONS: Nutrition has profound effects on microbial composition, in turn affecting wide-ranging metabolic, hormonal, and neurological processes. There is no consensus on what defines a "healthy" gut microbiome. Future research must consider individual responses to diet.
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Dieta , Microbioma Gastrointestinal , Humanos , Nutrientes , Fenómenos Fisiológicos de la NutriciónRESUMEN
PURPOSE OF REVIEW: The purpose of this review is to describe the trends in dietary patterns and food quality over time along with the possible role of ultra-processed foods in obesity, chronic diseases, and all-cause mortality in the US population. RECENT FINDINGS: There is a rising obesity epidemic, corresponding chronic diseases, and increases in ultra-processed food consumption. In mice and in vitro trials, emulsifiers, found in processed foods, have been found to alter microbiome compositions, elevate fasting blood glucose, cause hyperphagia, increase weight gain and adiposity, and induce hepatic steatosis. Recent human trials have found ultra-processed foods as a contributor to decreased satiety, increased meal eating rates, worsening biochemical markers, and more weight gain. In contrast, Blue Zone, indigenous South American, and Mediterranean populations with low meat intake, high fiber, and minimally processed foods have far less chronic diseases, obesity rates, and live longer disease-free. As the USA continues to industrialize, food has become more processed and cheaper and more convenient along with the coexistent rise in obesity prevalence. This review highlights the overall trends in food: mild improvements in dietary quality in higher socioeconomic populations, but no significant increases in whole fruit, vegetables, legumes, or nuts. Consumption of ultra-processed food is associated with weight gain and may contribute to metabolic syndrome and chronic disease. To combat this epidemic, we must create and disseminate detailed recommendations to improve diet quality and overall nutrition.
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History has shown that without explicit and enforced guidelines, even well-intentioned researchers can fail to adequately examine the ethical pros and cons of study design choices. One area in which consensus does not yet exist is the use of placebo groups in vitamin supplementation studies. As a prime example, we focus on vitamin D research. We aim to provide an overview of the ethical issues in placebo-controlled studies and guide future discussion about the ethical use of placebo groups. Research in the field of vitamin D shows variation in how placebo groups are used. We outline four types of control groups in use: active-control, placebo-control with restrictions on supplementation, placebo-control without supplementation restrictions, and placebo-control with rescue repletion therapy. The first two types highlight discrete ethical issues: active-control trials limit the ability to detect a difference; placebo-control trials that restrict supplementation potentially place subjects at risk of undue harm. The final two, placebo-control without supplementation restrictions or with rescue repletion therapy, offer potential solutions to these ethical challenges. Building on this, guidelines should be established and enforced on the use of placebo in supplementation studies. Furthermore, the field of vitamin D research has the potential to set an example worthy of emulation.
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Suplementos Dietéticos , Ensayos Clínicos Controlados Aleatorios como Asunto , Deficiencia de Vitamina D/dietoterapia , Vitamina D/uso terapéutico , Privación de Tratamiento , Humanos , Placebos , Guías de Práctica Clínica como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto/ética , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Proyectos de Investigación/normas , Índice de Severidad de la Enfermedad , Deficiencia de Vitamina D/fisiopatología , Privación de Tratamiento/ética , Privación de Tratamiento/normasRESUMEN
BACKGROUND AND AIMS: Partially covered self-expandable metallic stents (PCSEMS), although an effective treatment for anastomotic/staple line leaks and strictures, can be difficult to remove. This study examines the effectiveness of the inversion technique for the removal of PCSEMS in the treatment of leaks and strictures that occurred post-sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). METHODS: Consecutive patients who underwent PCSEMS removal for a leak and/or stricture post-SG or RYGB between July 2013 and December 2016 at the Johns Hopkins Medical Institutions were reviewed. All PCSEMS removals were first attempted via the inversion technique, which involves grasping the distal end of the stent and inverting it through itself. RESULTS: Fourteen patients (four males) underwent PCSEMS removal via the inversion technique for an anastomotic/staple line leak (50%), stricture (29%) or both (21%) post-SG (79%) or RYGB (21%). Technical success (successful removal of the stent) was achieved in one endoscopic session for 13 of the 14 PCSEMS (93%). One PCSEMS required the use of the stent-in-stent technique for removal. The median dwell time was 47 days (range 5-72). A distal partial occlusion developed in five patients (35%) due to tissue overgrowth and one PCSEMS (7%) migrated, necessitating premature removal. Eight patients (57%) experienced clinical success at follow-up, and six patients (43%) required subsequent treatment due to persistence or recurrence of the pathology. CONCLUSIONS: The inversion technique is a safe, effective, and efficient method of removing PCSEMS placed to correct anastomotic/staple line leaks and strictures post-SG and RYGB.
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Fuga Anastomótica/etiología , Fuga Anastomótica/cirugía , Remoción de Dispositivos/métodos , Endoscopía Gastrointestinal , Gastrectomía/efectos adversos , Derivación Gástrica/efectos adversos , Obesidad Mórbida/cirugía , Stents Metálicos Autoexpandibles , Adulto , Anciano , Constricción Patológica/cirugía , Remoción de Dispositivos/efectos adversos , Endoscopía Gastrointestinal/instrumentación , Endoscopía Gastrointestinal/métodos , Femenino , Gastrectomía/instrumentación , Gastrectomía/métodos , Derivación Gástrica/instrumentación , Derivación Gástrica/métodos , Humanos , Masculino , Persona de Mediana Edad , Reoperación/instrumentación , Reoperación/métodos , Estudios Retrospectivos , Grapado Quirúrgico/efectos adversos , Grapado Quirúrgico/instrumentación , Resultado del TratamientoRESUMEN
RATIONALE: Obstructive sleep apnea is associated with insulin resistance and liver injury. It is unknown whether apnea contributes to insulin resistance and steatohepatitis in severe obesity. OBJECTIVES: To examine whether sleep apnea and nocturnal hypoxemia predict the severity of insulin resistance, systemic inflammation, and steatohepatitis in severely obese individuals presenting for bariatric surgery. METHODS: We performed sleep studies and measured fasting blood glucose, serum insulin, C-reactive protein, and liver enzymes in 90 consecutive severely obese individuals, 75 women and 15 men, without concomitant diabetes mellitus or preexistent diagnosis of sleep apnea or liver disease. Liver biopsies (n = 20) were obtained during bariatric surgery. MEASUREMENTS AND MAIN RESULTS: Obstructive sleep apnea with a respiratory disturbance index greater than 5 events/hour was diagnosed in 81.1% of patients. The median respiratory disturbance index was 15 +/- 29 events/hour and the median oxygen desaturation during apneic events was 4.6 +/- 1.8%. All patients exhibited high serum levels of C-reactive protein, regardless of the severity of apnea, whereas liver enzymes were normal. Oxygen desaturation greater than 4.6% was associated with a 1.5-fold increase in insulin resistance, according to the homeostasis model assessment index. Histopathology data suggested that significant nocturnal desaturation might predispose to hepatic inflammation, hepatocyte ballooning, and liver fibrosis. Fasting blood glucose levels and steatosis scores were not affected by nocturnal hypoxia. There was no relationship between the respiratory disturbance index and insulin resistance or liver histopathology. CONCLUSIONS: Hypoxic stress of sleep apnea may be implicated in the development of insulin resistance and steatohepatitis in severe obesity.