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Estudios y lecturas de interés

Managing Metastatic Thymoma With Metabolic and Medical Therapy: A Case Report

Matthew C. L. Phillips (Department of Neurology,Waikato Hospital, Hamilton, New Zealand)

Deborah K. J. Murtagh (Healthy Kitchen Christchurch Ltd., Hamilton, New Zealand)

Sanjay K. Sinha (Department of Pathology, Waikato Hospital, Hamilton, New Zealand)

Ben G. Moon (Department of Radiology, Waikato Hospital, Hamilton, New Zealand)

5 may 2020

Thymomas consist of neoplastic thymic cells intermixed with variable numbers of non-neoplastic lymphocytes. Metastatic thymomas are typically managed with non-curative chemotherapy to control tumor-related symptoms; no prolonged survival is expected. Metabolic-based approaches, such as fasting and ketogenic diets, target cancer cell metabolism by creating an increased reliance on ketones while decreasing glucose, glutamine, and growth factor availability, theoretically depriving cancer cells of their metabolic fuels while creating an unfavorable environment for cancer growth, which may be beneficial in metastatic thymoma. We report the case of a 37-year-old woman with myasthenia gravis, diagnosed with an inoperable type AB, stage IVA thymoma, who pursued a metabolic intervention consisting of periodic fasting (7-day, fluid-only fasts every 1–2 months), combined with a modified ketogenic diet on feeding days, for 2 years. Fasting-related adverse effects included cold intolerance, fatigue, and generalized muscle aches, all of which resolved during the second year. She experienced two myasthenia relapses, each associated with profoundly reduced oral intake, marked weight loss, and tumor regression-the first relapse was followed by a 32% decrease in tumor volume over 4 months, the second relapse by a dramatic 96% decrease in tumor volume over 4 months. The second relapse also required prednisone to control the myasthenia symptoms. We hypothesize that 2 years of fasting and ketogenic diet therapy metabolically weakened the neoplastic thymic cell component of the thymoma, “setting the stage” for immune activation and extreme energy restriction to destroy the majority of cancer cells during both relapses, while prednisone-induced apoptosis eradicated the remaining lymphocytic component of the thymoma during the second relapse. This case is unique in that a metabolic-based fasting and ketogenic diet intervention was used as the primary management strategy for a metastatic cancer in the absence of surgery, chemotherapy, or radiotherapy, culminating in a near-complete regression. Nearly 3 years after being diagnosed with inoperable metastatic cancer, our patient shows no signs of disease and leads a full and active life.


Metastatic Thymoma, Fasting, Ketogenic Diet, Prednisone, Cancer

Dietary Guidelines Experts Again Condemn Saturated Fats, Ignore Rigorous Evidence

Nina Teicholz

1 may 2020

Last week, the USDA released its draft conclusions for the 2020 Dietary Guidelines for Americans (DGA), and the cap on saturated fats looks likely to stay firmly in place. The evidence linking saturated fats to heart disease was judged to be “strong,” not only for adults, but also, for the first time, children. These were the conclusions of the Subcommittee on Dietary Fats and Seafood, part of the larger DGA Advisory Committee.

The draft conclusions are not surprising, given that the five-person Subcommittee is one-sided and unbalanced, according to an analysis by the Nutrition Coalition. The group includes one of the staunchest foes of saturated fats and not a single person to oppose her. The conclusions are also unsurprising given that advice to limit saturated fat has been in place for 40 years. These views are entrenched in government agencies, university nutrition departments and are supported by many food and pharmaceutical interests.


Dietary Guidelines, Saturated Fats

Diabetes Canada Position Statement on Low Carbohydrate Diets for Adults with Diabetes: A Rapid Review

Canadian Journal of Diabetes

24 abr 2020

The aim of this position statement was to examine and appraise the current literature in order to identify a rational and safe approach to the use of low-CHO diets in people with diabetes, informed by current evidence, and to provide practical recommendations to patients and their health-care providers. This comprehensive literature search and study selection resulted in 33 relevant articles examining the role of very low-CHO and low-CHO diets in the management of type 1 and type 2 diabetes.


Diabetes, Low Carbohydrate Diets, Type 2 Diabetes, Type 1 Diabetes, Antihyperglycemic Therapies, Hypoglycemia, Healthy Nutrition

Intermittent fasting from dawn to sunset for 30 consecutive days is associated with anticancer proteomic signature and upregulates key regulatory proteins of glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system and cognitive function in healthy subjects

Ayse L.Mindikoglu, Mustafa M. Abdulsada, Antrix Jain, Jong Min Choi, Prasun K. Jalal, Sridevi Devaraj, Melissa P. Mezzari, Joseph F. Petrosino, Antone R. Opekun, Sung Yun Jung.

15 abr 2020

Abstract: Murine studies showed that disruption of circadian clock rhythmicity could lead to cancer and metabolic syndrome. Time-restricted feeding can reset the disrupted clock rhythm, protect against cancer and metabolic syndrome. Based on these observations, we hypothesized that intermittent fasting for several consecutive days without calorie restriction in humans would induce an anticarcinogenic proteome and the key regulatory proteins of glucose and lipid metabolism. Fourteen healthy subjects fasted from dawn to sunset for over 14 h daily. Fasting duration was 30 consecutive days. Serum samples were collected before 30-day intermittent fasting, at the end of 4th week during 30-day intermittent fasting, and one week after 30-day intermittent fasting. An untargeted serum proteomic profiling was performed using ultra high-performance liquid chromatography/tandem mass spectrometry. Our results showed that 30-day intermittent fasting was associated with an anticancer serum proteomic signature, upregulated key regulatory proteins of glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system, and cognitive function, and resulted in a serum proteome protective against cancer, metabolic syndrome, inflammation, Alzheimer's disease, and several neuropsychiatric disorders. These findings suggest that fasting from dawn to sunset for 30 consecutive days can be preventive and adjunct therapy in cancer, metabolic syndrome, and several cognitive and neuropsychiatric diseases.

Significance: Our study has important clinical implications. Our results showed that intermittent fasting from dawn to sunset for over 14 h daily for 30 consecutive days was associated with an anticancer serum proteomic signature and upregulated key regulatory proteins of glucose and lipid metabolism, insulin signaling, circadian clock, DNA repair, cytoskeleton remodeling, immune system, and cognitive function, and resulted in a serum proteome protective against cancer, obesity, diabetes, metabolic syndrome, inflammation, Alzheimer's disease, and several neuropsychiatric disorders. Importantly, these findings occurred in the absence of any calorie restriction and significant weight loss. These findings suggest that intermittent fasting from dawn to sunset can be a preventive and adjunct therapy in cancer, metabolic syndrome and Alzheimer's disease and several neuropsychiatric diseases.


Intermittent fasting, anticancer proteomic, circadian clock, DNA repair, cytoskeleton remodeling, immune system, cognitive function, cancer, metabolic syndrome, Alzheimer's disease, several neuropsychiatric diseases

Low-Carbohydrate Diets in the Management of Obesity and Type 2 Diabetes: A Review from Clinicians Using the Approach in Practice

Tara Kelly (HRB Clinical Research Facility, National University of Ireland, H91YR71 Galway, Ireland)

David Unwin (The Norwood Surgery, Southport PR9 7EG, UK)

Francis Finucane (HRB Clinical Research Facility, National University of Ireland, H91YR71 Galway, Ireland) (Bariatric Medicine Service, Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, H91YR71 Galway, Ireland)

8 abr 2020

​Low-carbohydrate diets are increasingly used to help patients with obesity and type 2 diabetes. We sought to provide an overview of the evidence for this treatment approach, considering the epidemiology and pathophysiology of obesity and diabetes in terms of carbohydrate excess. We describe the mechanistic basis for the clinical benefits associated with nutritional ketosis and identify areas of practice where the evidence base could be improved. We summarize the key principles which inform our approach to treating patients with low-carbohydrate diets. The scientific controversy relating to these diets is real but is consistent with the known challenges of any dietary interventions and also the limitations of nutritional epidemiology. Secondly, notwithstanding any controversy, international guidelines now recognize the validity and endorse the use of these diets as a therapeutic nutritional approach, in appropriate patients. Thirdly, we have found that early de-prescription of diabetes medications is essential, in particular insulin, sulphonylureas, and sodium-glucose cotransporter (SGLT2) inhibitors. Fourthly, we encourage patients to eat ad libitum to satiety, rather than calorie counting per se. Furthermore, we monitor cardiovascular risk factors frequently, as with all patients with obesity or diabetes, but we do not necessarily consider an increase in low-density lipoprotein (LDL)-cholesterol as an absolute indication to stop these diets, as this is usually related to large LDL particles, which are not associated with increased cardiovascular risk. In the absence of large randomized controlled trials with cardiovascular and other hard endpoints, adopting a low-carbohydrate diet is a legitimate and potentially effective treatment option for patients with diabetes or obesity.


low-carbohydrate diets; diabetes remission; lifestyle modification; obesity treatment; type 2 diabetes

Glycaemic stability of a cyclist with Type 1 diabetes: 4011 km in 20 days on a ketogenic diet

Nolan J, Rush A, Kaye J. (Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands. Type 1 Diabetes Family Centre, Osborne Park, WA, Australia)

4 jul 2019

BACKGROUND: Maintaining glycaemic control during exercise presents a significant challenge for people living with Type 1 diabetes. Significant glycaemic variability has been observed in athletes with Type 1 diabetes in competitive contexts. While very-low-carbohydrate ketogenic diets have been shown to minimize glycaemic excursions, no published data have examined if this translates to exercise.

CASE REPORT: We report the case of a 37-year-old man with Type 1 diabetes who successfully undertook a 4011 km cycle across Australia over 20 consecutive days whilst consuming a very-low-carbohydrate ketogenic diet. Continuous glucose monitoring data capture was 98.4% for the ride duration and showed remarkable glycaemic stability, with a standard deviation of 2.1 mmol/l (average interstitial glucose 6.1 mmol/l) and 80.4% of time spent within a range of 3.9-10 mmol/l. Interstitial glucose was <3 mmol/l for 2.1% of this time, with only a single episode of symptomatic hypoglycaemia prompting brief interruption of exercise for carbohydrate administration.

CONCLUSION: This case demonstrates the viability of a very-low-carbohydrate ketogenic diet in an individual with Type 1 diabetes undertaking exercise. While the effect of a very-low-carbohydrate ketogenic diet is yet to be examined more broadly in athletes with Type 1 diabetes, the glycaemic stability observed suggests that fat adaptation may attenuate glycaemic swings and reduce reliance on carbohydrate consumption during exercise for maintaining euglycaemia.


Type 1 diabetes, ketogenic diet, Glycaemic stability

Prevalence of Optimal Metabolic Health in American Adults: National Health and Nutrition Examination Survey 2009–2016

Joana Araújo, Jianwen Cai and June Stevens.

8 feb 2019

Background: Several guidelines for cardiometabolic risk factor identification and management have been released in recent years, but there are no estimates of current prevalence of metabolic health among adults in the United States. We estimated the proportion of American adults with optimal cardiometabolic health, using different guidelines.

Methods: Data from the National Health and Nutrition Examination Survey 2009–2016 were analyzed (n = 8721). Using the most recent guidelines, metabolic health was defined as having optimal levels of waist circumference (WC <102/88 cm for men/women), glucose (fasting glucose <100 mg/dL and hemoglobin A1c <5.7%), blood pressure (systolic <120 and diastolic <80 mmHg), triglycerides (<150 mg/dL), and high-density lipoprotein cholesterol (≥40/50 mg/dL for men/women), and not taking any related medication.

Results: Changing from ATP III (Adult Treatment Panel III) guidelines to more recent cut points decreased the proportion of metabolically healthy Americans from 19.9% (95% confidence interval [CI]: 18.3–21.5) to 12.2% (95% CI: 10.9–13.6). Dropping WC from the definition increased the percentage of adults with optimal metabolic health to 17.6%. Characteristics associated with greater prevalence of metabolic health were female gender, youth, more education, never smoking, practicing vigorous physical activity, and low body mass index. Less than one-third of normal weight adults were metabolically healthy and the prevalence decreased to 8.0% and 0.5% in overweight and obese individuals, respectively.

Conclusions: Prevalence of metabolic health in American adults is alarmingly low, even in normal weight individuals. The large number of people not achieving optimal levels of risk factors, even in low-risk groups, has serious implications for public health.


Metabolic Health, Health and Nutrition,

Anticatabolic Effects of Ketone Bodies in Skeletal Muscle

Koutnik AP., D'Agostino DP., Egan B. (Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA. National Institute for Cellular Biotechnology, School of Health and Human Performance, Dublin City University, Glasnevin, Dublin 9, Ireland)

31 ene 2019

The ketone bodies acetoacetate (AcAc) and β-hydroxybutyrate (βHB) are the subject of renewed interest given recently established pleiotropic effects regulating inflammation, oxidative stress, and gene expression. Anticatabolic effects of β-hydroxybutyrate have recently been demonstrated in human skeletal muscle under inflammatory insult, thereby expanding upon the wide-ranging therapeutic applications of nutritional ketosis.


acetoacetate; atrophy; cachexia; inflammation; muscle protein breakdown; β-hydroxybutyrate

Only 12 percent of American adults are metabolically healthy, study finds

University of North Carolina at Chapel Hill

28 nov 2018

The prevalence of metabolic health in American adults is 'alarmingly low,' even among people who are normal weight, according to a new study from the University of North Carolina at Chapel Hill's Gillings School of Global Public Health. Only one in eight Americans is achieving optimal metabolic health. This carries serious implications for public health since poor metabolic health leaves people more vulnerable to developing Type 2 diabetes, cardiovascular disease and other serious health issues.


Type 2 Diabetes, Healthy Nutrition, metabolic syndrome, Metabolic Health

Ketogenic Medium Chain Triglycerides Increase Brain Energy Metabolism in Alzheimer's Disease

Croteau E., Castellano CA., Richard MA., Fortier M., Nugent S., Lepage M., Duchesne S.,

Whittingstall K., Turcotte ÉE., Bocti C., Fülöp T., Cunnane SC.

20 jun 2018

BACKGROUND: In Alzheimer's disease (AD), it is unknown whether the brain can utilize additional ketones as fuel when they are derived from a medium chain triglyceride (MCT) supplement.

OBJECTIVE: To assess whether brain ketone uptake in AD increases in response to MCT as it would in young healthy adults.

METHODS: Mild-moderate AD patients sequentially consumed 30 g/d of two different MCT supplements, both for one month: a mixture of caprylic (55%) and capric acids (35%) (n = 11), followed by a wash-out and then tricaprylin (95%; n = 6). Brain ketone (11C-acetoacetate) and glucose (FDG) uptake were quantified by PET before and after each MCT intervention.

RESULTS: Brain ketone consumption doubled on both types of MCT supplement. The slope of the relationship between plasma ketones and brain ketone uptake was the same as in healthy young adults. Both types of MCT increased total brain energy metabolism by increasing ketone supply without affecting brain glucose utilization.

CONCLUSION: Ketones from MCT compensate for the brain glucose deficit in AD in direct proportion to the level of plasma ketones achieved.


Alzheimer's disease, MCT, Medium Chain Triglycerides, Ketogenic, ketone

Ketogenic diet, high intensity interval training (HIIT) and memory training in the treatment of mild cognitive impairment: A case study.

Dahlgren K., Gibas KJ. (Human Bioenergetics & Applied Health Science, Bethel University, MN, USA)

11 abr 2018

Alzheimer's disease (AD) deaths have increased by 89% since 2000. This alarming trajectory of neurological disease highlights the failure of current best practice. Deteriorating brain fuel supply is the nemesis of intact neurological health. Cerebral hypo-metabolism associated with AD occurs years before onset. Both the ketogenic diet and calorie restriction (fasting) lead to a compensatory rise in ketones to improve energy deficits in the brain derived from cerebral insulin resistance. Two forms of ketone bodies, β-hydroxybutyrate and acetoacetate, fuel the brain during starvation, fasting and strenuous exercise. Ketones are neuroprotective agents that shelter the aging brain from memory loss and neurodegeneration. Induced ketone production has been shown to ameliorate mitochondrial function, reduce the expression of apoptotic and inflammatory mediators and provide neuroprotection to cells (Lange et al., 2017). This case study highlights an innovative research design aimed at attenuating memory decline in a 57 year old female previously diagnosed with comorbid mild cognitive impairment (MCI) and metabolic syndrome (MetS). Mild cognitive impairment is a predementia syndrome known to precede AD (Michaud et al, 2017). The 12-week intervention included ketogenic nutrition protocol, high intensity interval training (HIIT) and memory training using the PEAK brain training app. Memory function was assessed via the MoCA (Montreal Cognitive Assessment) pre/post intervention. Physiological biomarkers for MetS including HOMA-IR(homeostatic model assessment of insulin resistance), triglyceride/HDL ratio, HgA1c, fasting triglycerides and HDL were measured pre/post intervention. MoCA baseline score was 22/30 (MCI); post intervention score: 30/30 (normal). MetS biomarker improvements also reflected statistical significance.


Alzheimer’s disease; Ketogenic diet; Memory loss; Metabolic syndrome (MetS); Mild cognitive impairment (MCI); MoCA

Health Benefits of Fasting and Caloric Restriction

Saeid Golbidi, Andreas Daiber, Bato Korac, Huige Li, M. Faadiel Essop & Ismail Laher

23 oct 2017

Purpose of Review: Obesity and obesity-related diseases, largely resulting from urbanization and behavioral changes, are now of global importance. Energy restriction, though, is associated with health improvements and increased longevity. We review some important mechanisms related to calorie limitation aimed at controlling of metabolic diseases, particularly diabetes.

Recent Findings: Calorie restriction triggers a complex series of intricate events, including activation of cellular stress response elements, improved autophagy, modification of apoptosis, and alteration in hormonal balance. Intermittent fasting is not only more acceptable to patients, but it also prevents some of the adverse effects of chronic calorie restriction, especially malnutrition.

Summary: There are many somatic and potentially psychologic benefits of fasting or intermittent calorie restriction. However, some behavioral modifications related to abstinence of binge eating following a fasting period are crucial in maintaining the desired favorable outcomes.


Fasting, Caloric Restriction

The Ketogenic Diet: Making a Comeback

Walczyk T, Wick JY.

1 jul 2017

Americans have embraced a large number of diets in an attempt to manage obesity, improve quality of life, and address specific health problems. Among diets developed to address health problems, the ketogenic diet has had a long and variable history. Developed in the 1920s by a faith healer to help children with epilepsy, this diet induces a state that mimics carbohydrate starvation. As medications became available and effectively addressed seizures, the diet fell out of favor. During the last few decades, researchers and clinicians have learned that it can be useful in children and adults with refractory epilepsy and a variety of other conditions. Once again, pharmacists may encounter patients who are employing dietary management of serious health problems. This very high-fat diet almost eliminates carbohydrates from the patient's food selection. The result is the substitution of ketone bodies as a source of energy. Today's ketogenic diet has been modified with scientifically proven adjustments to increase palatability and help with adherence. Effective for some forms of epilepsy, the ketogenic diet also seems to have some utility in Alzheimer's disease, Parkinson's disease, and glaucoma, and many Americans are using it to lose weight. Consultant pharmacists may field questions about this diet, its potential to correct or alleviate health conditions, and its limitations. The article discusses the ketogenic diet's strengths, limitations, potential mechanisms, and use in a number of conditions with an emphasis on the elderly.


Ketogenic Diet, Epilepsy, Alzheimer's disease, Parkinson's disease, Glaucoma, lose weight

The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention

Michael F. Holick (Endocrinology, Nutrition and Diabetes, Department of Medicine, Boston University Medical Center, Boston, MA, 02118, USA)

17 may 2017

Vitamin D deficiency and insufficiency is a global health issue that afflicts more than one billion children and adults worldwide. The consequences of vitamin D deficiency cannot be under estimated. There has been an association of vitamin D deficiency with a myriad of acute and chronic illnesses including preeclampsia, childhood dental caries, periodontitis, autoimmune disorders, infectious diseases, cardiovascular disease, deadly cancers, type 2 diabetes and neurological disorders. This review is to put into perspective the controversy surrounding the definition for vitamin D deficiency and insufficiency as well as providing guidance for how to treat and prevent vitamin D deficiency.


Vitamin D deficiency, Vitamin D insufficiency, Sunlight, Rickets, Vitamin D2, Vitamin D3, 25-hydroxyvitamin D, Vitamin D toxicity

Ketogenic diet in migraine: rationale, findings and perspectives

Barbanti P, Fofi L, Aurilia C, Egeo G, Caprio M.

1 may 2017

Ketogenic diet (KD) is an established treatment for refractory pediatric epilepsy and a promising therapy for diverse neurological diseases. Clinical data on KD in migraine-obtained from 150 patients investigated in case reports and prospective studies-suggest that KD may be a rapid onset effective prophylaxis for episodic and chronic migraine. KD would contribute to restore brain excitability and metabolism and to counteract neuroinflammation in migraine, although its precise mechanism is still unclear. Randomized controlled studies are needed to confirm the usefulness of KD in migraine and to investigate its optimal duration, repeatability, feasibility in normal weight subjects, efficacy in pediatric population and association to conventional migraine prophylaxis.


Disability; Ketogenic diet; Migraine; Prevention; Treatment

Statins for Primary Prevention: The Debate Is Intense, but the Data Are Weak

Rita F. Redberg, MD, Mitchell H. Katz, MD.

15 nov 2016

This issue of JAMA contains the latest US Preventive Services Task Force (USPSTF) recommendation statement on statins for prevention of cardiovascular disease in adults,1 along with the accompanying evidence report and systematic review2 on which the recommendations are based. The evidence report summarized data from 19 trials including a total of 71 344 patients and concluded that statin therapy was associated with reduced risk of all-cause and cardiovascular mortality and cardiovascular disease (CVD) events. Thus, the task force recommended “initiating use of low- to moderate-dose statins in adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 10% or greater (B recommendation)” or “7.5% to 10% (C recommendation).”1 Although the task force did their usual careful job of reviewing the evidence, the evidence for treating asymptomatic persons with statins does not appear to merit a grade B or even a grade C recommendation.


Cardiology Cardiovascular, Risk Factors Clinical, Pharmacy and Pharmacology, Dyslipidemia

Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation

Mark Evans, Karl E. Cogan, Brendan Egan.

10 nov 2016

Optimising training and performance through nutrition strategies is central to supporting elite sportspeople, much of which has focused on manipulating the relative intake of carbohydrate and fat and their contributions as fuels for energy provision. The ketone bodies, namely acetoacetate, acetone and β‐hydroxybutyrate (βHB), are produced in the liver during conditions of reduced carbohydrate availability and serve as an alternative fuel source for peripheral tissues including brain, heart and skeletal muscle. Ketone bodies are oxidised as a fuel source during exercise, are markedly elevated during the post‐exercise recovery period, and the ability to utilise ketone bodies is higher in exercise‐trained skeletal muscle. The metabolic actions of ketone bodies can alter fuel selection through attenuating glucose utilisation in peripheral tissues, anti‐lipolytic effects on adipose tissue, and attenuation of proteolysis in skeletal muscle. Moreover, ketone bodies can act as signalling metabolites, with βHB acting as an inhibitor of histone deacetylases, an important regulator of the adaptive response to exercise in skeletal muscle. Recent development of ketone esters facilitates acute ingestion of βHB that results in nutritional ketosis without necessitating restrictive dietary practices. Initial reports suggest this strategy alters the metabolic response to exercise and improves exercise performance, while other lines of evidence suggest roles in recovery from exercise. The present review focuses on the physiology of ketone bodies during and after exercise and in response to training, with specific interest in exploring the physiological basis for exogenous ketone supplementation and potential benefits for performance and recovery in athletes.


Acetoacetate, β‐hydroxybutyrate, Ketosis, Performance, Substrate

Association of Higher Consumption of Foods Derived From Subsidized Commodities With Adverse Cardiometabolic Risk Among US Adults

Karen R. Siegel, PhD; Kai McKeever Bullard, PhD; Giuseppina Imperatore, MD.

5 jul 2016

Importance:  Food subsidies are designed to enhance food availability, but whether they promote cardiometabolic health is unclear.

Objective:  To investigate whether higher consumption of foods derived from subsidized food commodities is associated with adverse cardiometabolic risk among US adults.

Design, Setting, and Participants:  Cross-sectional analysis of the National Health and Nutrition Examination Survey data from 2001 to 2006. Our final analysis was performed in January 2016. Participants were 10 308 nonpregnant adults 18 to 64 years old in the general community.

Exposure:  From a single day of 24-hour dietary recall in the National Health and Nutrition Examination Survey, we calculated an individual-level subsidy score that estimated an individual’s consumption of subsidized food commodities as a percentage of total caloric intake.

Main Outcomes and Measures:  The main outcomes were body mass index (calculated as weight in kilograms divided by height in meters squared), abdominal adiposity, C-reactive protein level, blood pressure, non–high-density lipoprotein cholesterol level, and glycemia.

Results  Among 10 308 participants, the mean (SD) age was 40.2 (0.3) years, and a mean (SD) of 50.5% (0.5%) were male. Overall, 56.2% of calories consumed were from the major subsidized food commodities. United States adults in the highest quartile of the subsidy score (compared with the lowest) had increased probabilities of having a body mass index of at least 30 (prevalence ratio, 1.37; 95% CI, 1.23-1.52), a ratio of waist circumference to height of at least 0.60 (prevalence ratio, 1.41; 95% CI, 1.25-1.59), a C-reactive protein level of at least 0.32 mg/dL (prevalence ratio, 1.34; 95% CI, 1.19-1.51), an elevated non–high-density lipoprotein cholesterol level (prevalence ratio, 1.14; 95% CI, 1.05-1.25), and dysglycemia (prevalence ratio, 1.21; 95% CI, 1.04-1.40). There was no statistically significant association between the subsidy score and blood pressure.

Conclusions and Relevance:  Among US adults, higher consumption of calories from subsidized food commodities was associated with a greater probability of some cardiometabolic risks. Better alignment of agricultural and nutritional policies may potentially improve population health.


Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Diet

A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms

Choi IY, Piccio L, Childress P, Bollman B, Ghosh A, Brandhorst S, Suarez J, Michalsen A, Cross AH, Morgan TE, Wei M, Paul F, Bock M, Longo VD.

26 may 2016

Dietary interventions have not been effective in the treatment of multiple sclerosis (MS). Here, we show that periodic 3-day cycles of a fasting mimicking diet (FMD) are effective in ameliorating demyelination and symptoms in a murine experimental autoimmune encephalomyelitis (EAE) model. The FMD reduced clinical severity in all mice and completely reversed symptoms in 20% of animals. These improvements were associated with increased corticosterone levels and regulatory T (Treg) cell numbers and reduced levels of pro-inflammatory cytokines, TH1 and TH17 cells, and antigen-presenting cells (APCs). Moreover, the FMD promoted oligodendrocyte precursor cell regeneration and remyelination in axons in both EAE and cuprizone MS models, supporting its effects on both suppression of autoimmunity and remyelination. We also report preliminary data suggesting that an FMD or a chronic ketogenic diet are safe, feasible, and potentially effective in the treatment of relapsing-remitting multiple sclerosis (RRMS) patients (NCT01538355).

Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.


Diet Mimicking Fasting, Regeneration, Autoimmunity, Multiple Sclerosis, Remyelination, FMD, Ketogenic Diet

Head-to-head randomized trials are mostly industry sponsored and almost always favor the industry sponsor

Maria Elena Flacco,  Lamberto Manzoli, Stefania Boccia, Lorenzo Capasso, Katina Aleksovska, Annalisa Rosso, Giacomo Scaioli, Corrado De Vito, Roberta Siliquini, Paolo Villari, John P.A. Loannidis.

1 jul 2015

Objectives: To map the current status of head-to-head comparative randomized evidence and to assess whether funding may impact on trial design and results.

Study Design and Setting: From a 50% random sample of the randomized controlled trials (RCTs) published in journals indexed in PubMed during 2011, we selected the trials with ≥100 participants, evaluating the efficacy and safety of drugs, biologics, and medical devices through a head-to-head comparison.

Results: We analyzed 319 trials. Overall, 238,386 of the 289,718 randomized subjects (82.3%) were included in the 182 trials funded by companies. Of the 182 industry-sponsored trials, only 23 had two industry sponsors and only three involved truly antagonistic comparisons. Industry-sponsored trials were larger, more commonly registered, used more frequently noninferiority/equivalence designs, had higher citation impact, and were more likely to have “favorable” results (superiority or noninferiority/equivalence for the experimental treatment) than nonindustry-sponsored trials. Industry funding [odds ratio (OR) 2.8; 95% confidence interval (CI): 1.6, 4.7] and noninferiority/equivalence designs (OR 3.2; 95% CI: 1.5, 6.6), but not sample size, were strongly associated with “favorable” findings. Fifty-five of the 57 (96.5%) industry-funded noninferiority/equivalence trials got desirable “favorable” results.

Conclusion: The literature of head-to-head RCTs is dominated by the industry. Industry-sponsored comparative assessments systematically yield favorable results for the sponsors, even more so when noninferiority designs are involved.


Head-to-head comparison, Randomized controlled trials, Industry sponsorship, Noninferiority trials, Conflict of interest, Cross-sectional study

Food Order Has a Significant Impact on Postprandial Glucose and Insulin Levels

Alpana P. Shukla, Radu G. Iliescu, Catherine E. Thomas, and Louis J. Aronne.

11 jun 2015

Postprandial hyperglycemia is an important therapeutic target for optimizing glycemic control and for mitigating the proatherogenic vascular environment characteristic of type 2 diabetes. Existing evidence indicates that the quantity and type of carbohydrate consumed influence blood glucose levels and that the total amount of carbohydrate consumed is the primary predictor of glycemic response (1). Previous studies have shown that premeal ingestion of whey protein, as well as altering the macronutrient composition of a meal, reduces postmeal glucose levels (2–4). There are limited data, however, regarding the effect of food order on postprandial glycemia in patients with type 2 diabetes (5). In this pilot study, we sought to examine the effect of food order, using a typical Western meal, incorporating vegetables, protein, and carbohydrate, on postprandial glucose and insulin excursions in overweight/obese adults with type 2 diabetes.


Postprandial hyperglycemia, type 2 diabetes, glycemic control, Postprandial Glucose, Postprandial Insulin

Reduced carbohydrate availability enhances exercise-induced p53 signaling in human skeletal muscle: implications for mitochondrial biogenesis

Jonathan D. Bartlett, Jari Louhelainen, Zafar Iqbal, Andrew J. Cochran, Martin J. Gibala, Warren Gregson, Graeme L. Close, Barry Drust, and James P. Morton.

15 mar 2013

Perspectives and Significance: We present novel data by demonstrating that exercise-induced p53 phosphorylation in human skeletal muscle appears dependent on CHO availability, which may be regulated, in part, through upstream signaling by AMPK. Given the emergence of p53 as a regulator of mitochondrial biogenesis in skeletal muscle (34, 47), the nutritional modulation of contraction-induced p53 activation is likely to have implications for both athletic and clinical populations. Indeed, numerous investigators have demonstrated a functional role of p53 in improving physical performance, as demonstrated by improved exercise capacity in wild-type animals compared with p53 knockout animals during fatiguing swimming (30), treadmill running (34), and electrical stimulation (47) protocols. Furthermore, considering the role of p53 in promoting a shift from glycolysis toward lipid metabolism (6) and the fact that training with reduced CHO availability promotes lipid utilization during submaximal exercise (21, 63), early signaling through p53 may, therefore, represent an additional potential signaling pathway which regulates oxidative adaptations to endurance training (i.e., increased mitochondrial volume and shifts in substrate utilization), thereby exerting potent effects on subsequent endurance performance. Moreover, because reduced p53 function is associated with tumor development (28), insulin resistance (3), and reduced longevity (29), the combined effects of exercise and low CHO availability on p53 activity, therefore, represents potential exercise interventions to improve various indices of human health. Clearly, further longitudinal studies examining the physiological function of p53 in human cells and tissues are now warranted.


AMPK, PGC-1α, glycogen, high-intensity interval running

Lifestyle Coaching: A Different Approach to Fitness Success

Chris McGrath, James Beauchemin.

8 dic 2011

While the fitness industry has grown significantly over the past twenty years, obesity rates and lifestyle-related health issues continue to climb. If providing "state of the art" exercise facilities with "cutting edge" exercise programming were the answer, we as an industry should have helped significantly reduce these issues by now. But this has yet to happen. For millions seeking healthy change, a different approach is needed. One approach that has quietly emerged to address these issues is lifestyle coaching — or, as it also known, health and/or wellness coaching.

Lifestyle coaching uses a sophisticated combination of interviewing skills and goal-setting strategies to lead clients to manage healthier behaviors. While lifestyle coaching will follow a similar process, it is not to be confused with life coaching. Life coaching typically addresses personal development matters including career, relationships, and spirituality. Lifestyle coaching, in contrast, focuses directly on matters that influence physical and mental health by helping clients to cultivate a “mind-body” relationship while providing guidance in the three major areas of overall wellness: exercise, nutrition and stress management. The “mind-body” or “holistic” approach to wellness utilizes an approach that is “grounded in the powerful ways in which your body, thoughts, emotions, social, and behavioral factors can directly affect each other” (Ray, 2004). This can lead to lasting improvements and establish lifestyle trends where traditional training has fallen short.


Lifestyle Coaching

Metabolic adaptation at birth

Martin Ward Platt, Sanjeev Deshpande.

1 abr 2005

After birth, the neonate must make a transition from the assured continuous transplacental supply of glucose to a variable fat-based fuel economy. The normal infant born at term accomplishes this transition through a series of well-coordinated metabolic and hormonal adaptive changes. The patterns of adaptation in the preterm infant and the baby born after intrauterine growth restriction are, however, different to that of a full-term neonate, with the risk for former groups that there will be impaired counter-regulatory ketogenesis. There is much less precise linkage of neonatal insulin secretion to prevailing blood glucose concentrations. These patterns of metabolic adaptation are further influenced by feeding practices.


Adaptation Physiological, Blood Glucose, Bottle Feeding, Breast Feeding, Glucose, Metabolism, Homeostasis, Physiology, Infant, Newborn, Insulin, Insulin Secretion, Ketone Bodies

Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids

Institute of Medicine; Food and Nutrition Board; Panel on Macronutrients; Panel on the Definition of Dietary Fiber; Subcommittee on Upper Reference Levels of Nutrients; Subcommittee on Interpretation and Uses of Dietary Reference Intakes; Standing Committee on the Scientific Evaluation of Dietary Reference Intakes

1 ene 2005

Responding to the expansion of scientific knowledge about the roles of nutrients in human health, the Institute of Medicine has developed a new approach to establish Recommended Dietary Allowances (RDAs) and other nutrient reference values. The new title for these values Dietary Reference Intakes (DRIs), is the inclusive name being given to this new approach. These are quantitative estimates of nutrient intakes applicable to healthy individuals in the United States and Canada. This new book is part of a series of books presenting dietary reference values for the intakes of nutrients. It establishes recommendations for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. This book presents new approaches and findings which include the following:


Food and Nutrition, Nutrition, Dietary Reference Intakes

Hyperinsulinemia and risk of Alzheimer disease

Jose A. Luchsinger, Ming-Xin Tang, Steven Shea, Richard Mayeux

12 oct 2004

Objective: To explore the association between fasting insulin levels and dementia.

Methods: Fasting insulin levels were measured from frozen sera using solid-phase chemiluminescent enzyme immunoassay in a sample of elderly subjects chosen at random from a cohort of persons aged 65 years and older from northern Manhattan. Dementia was diagnosed using standard methods. Neuropsychiatric testing was available on all subjects at each follow-up interval.

Results: A total of 683 subjects without prevalent dementia were followed for 3,691 person-years and 149 persons developed dementia (137 Alzheimer disease [AD], 6 dementia associated with stroke, 6 other). The risk of AD doubled in the 39% of the sample with hyperinsulinemia (HR = 2.1; 95% CI: 1.5, 2.9) and was highest in people without diabetes. The HR relating presence of hyperinsulinemia or diabetes in 50% of our sample to AD was 2.2 (95% CI: 1.5, 3.1). The risk of AD attributable to the presence of hyperinsulinemia or diabetes was 39%. The HR of AD for the highest quartile of insulin compared to the lowest was 1.7 (95% CI: 1.0, 2.7; p for trend = 0.009). Hyperinsulinemia was also related to a significant decline in memory-related cognitive scores, but not to decline in other cognitive domains.

Conclusions: Hyperinsulinemia is associated with a higher risk of AD and decline in memory.


Neurology, Hyperinsulinemia, Alzheimer, Dementia, Neuropsychiatric, Diabetes

"A Calorie Is a Calorie" Violates the Second Law of Thermodynamics

Richard D Feinman, Eugene J Fine.

28 jul 2004

The principle of "a calorie is a calorie," that weight change in hypocaloric diets is independent of macronutrient composition, is widely held in the popular and technical literature, and is frequently justified by appeal to the laws of thermodynamics. We review here some aspects of thermodynamics that bear on weight loss and the effect of macronutrient composition. The focus is the so-called metabolic advantage in low-carbohydrate diets--greater weight loss compared to isocaloric diets of different composition. Two laws of thermodynamics are relevant to the systems considered in nutrition and, whereas the first law is a conservation (of energy) law, the second is a dissipation law: something (negative entropy) is lost and therefore balance is not to be expected in diet interventions. Here, we propose that a misunderstanding of the second law accounts for the controversy about the role of macronutrient effect on weight loss and we review some aspects of elementary thermodynamics. We use data in the literature to show that thermogenesis is sufficient to predict metabolic advantage. Whereas homeostasis ensures balance under many conditions, as a general principle, "a calorie is a calorie" violates the second law of thermodynamics.



Effects of Strength Training on Muscle Power and Serum Hormones in Middle-Aged and Older Men

M Izquierdo, K Häkkinen, J Ibañez, M Garrues, A Antón, A Zúñiga, J L Larrión, E M Gorostiaga.

1 abr 2001

Effects of 16-wk strength training on maximal strength and power performance of the arm and leg muscles and serum concentrations [testosterone (T), free testosterone (FT), and cortisol] were examined in 11 middle-aged (M46; 46 ± 2 yr) and 11 older men (M64; 64 ± 2 yr). During the 16-wk training, the relative increases in maximal strength and muscle power output of the arm and leg muscles were significant in both groups (P < 0.05–0.001), with no significant differences between the two groups. The absolute increases were higher (P < 0.01–0.05) in M46 than in M64 mainly during the last 8 wk of training. No significant changes were observed for serum T and FT concentrations. Analysis of covariance showed that, during the 16-wk training period, serum FT concentrations tended to decrease in M64 and increase in M46 (P < 0.05). However, significant correlations between the mean level of individual serum T and FT concentrations and the individual changes in maximal strength were observed in a combined group during the 16-wk training (r = 0.49 and 0.5, respectively; P < 0.05). These data indicate that a prolonged total strength-training program would lead to large gains in maximal strength and power load characteristics of the upper and lower extremity muscles, but the pattern of maximal and power development seemed to differ between the upper and lower extremities in both groups, possibly limited in magnitude because of neuromuscular and/or age-related endocrine impairments.


Aging, Maximal strength, Muscle power, Testosterone

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