A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease

Posted on January 15, 2016 by Maurice Preter MD

A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease

http://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-2-28

  • Ingrid Van der Auwera,
  • Stefaan Wera,
  • Fred Van Leuven et al.
Nutrition & Metabolism20052:28

Abstract

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that primarily strikes the elderly. Studies in both humans and animal models have linked the consumption of cholesterol and saturated fats with amyloid-β (Aβ) deposition and development of AD. Yet, these studies did not examine high fat diets in combination with reduced carbohydrate intake. Here we tested the effect of a high saturated fat/low carbohydrate diet on a transgenic mouse model of AD.

Results

Starting at three months of age, two groups of female transgenic mice carrying the “London” APP mutation (APP/V717I) were fed either, a standard diet (SD) composed of high carbohydrate/low fat chow, or a ketogenic diet (KD) composed of very low carbohydrate/high saturated fat chow for 43 days. Animals fed the KD exhibited greatly elevated serum ketone body levels, as measured by β-hydroxybutyrate (3.85 ± 2.6 mM), compared to SD fed animals (0.29 ± 0.06 mM). In addition, animals fed the KD lost body weight (SD 22.2 ± 0.6 g vs. KD 17.5 ± 1.4 g, p = 0.0067). In contrast to earlier studies, the brief KD feeding regime significantly reduced total brain Aβ levels by approximately 25%. Despite changes in ketone levels, body weight, and Aβ levels, the KD diet did not alter behavioral measures.

Conclusion

Previous studies have suggested that diets rich in cholesterol and saturated fats increased the deposition of Aβ and the risk of developing AD. Here we demonstrate that a diet rich in saturated fats and low in carbohydrates can actually reduce levels of Aβ. Therefore, dietary strategies aimed at reducing Aβ levels should take into account interactions of dietary components and the metabolic outcomes, in particular, levels of carbohydrates, total calories, and presence of ketone bodies should be considered.

 

 

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Neuroprotective and disease-modifying effects of the ketogenic diet

Posted on January 15, 2016 by Maurice Preter MD

Neuroprotective and disease-modifying effects of the ketogenic diet

Behav Pharmacol. Author manuscript; available in PMC 2008 May 5.
 
Published in final edited form as:

 

Reading it again.. Well worth it.

Abstract

The ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy. A recent clinical study has raised the possibility that exposure to the ketogenic diet may confer long-lasting therapeutic benefits for patients with epilepsy. Moreover, there is evidence from uncontrolled clinical trials and studies in animal models that the ketogenic diet can provide symptomatic and disease-modifying activity in a broad range of neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease, and may also be protective in traumatic brain injury and stroke. These observations are supported by studies in animal models and isolated cells that show that ketone bodies, especially β-hydroxybutyrate, confer neuroprotection against diverse types of cellular injury. This review summarizes the experimental, epidemiological and clinical evidence indicating that the ketogenic diet could have beneficial effects in a broad range of brain disorders characterized by the death of neurons. Although the mechanisms are not yet well defined, it is plausible that neuroprotection results from enhanced neuronal energy reserves, which improve the ability of neurons to resist metabolic challenges, and possibly through other actions including antioxidant and anti-inflammatory effects. As the underlying mechanisms become better understood, it will be possible to develop alternative strategies that produce similar or even improved therapeutic effects without the need for exposure to an unpalatable and unhealthy, high-fat diet.

Keywords: Alzheimer’s disease, cellular energetics, epilepsy, ketone bodies, ketogenic diet, mitochondria, neuroprotection, Parkinson’s disease, stroke, traumatic brain injury
 
 
 
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Crowdsourcing Diagnosis for Patients With Undiagnosed Illnesses: An Evaluation of CrowdMed

Posted on January 15, 2016 by Maurice Preter MD

Crowdsourcing Diagnosis for Patients With Undiagnosed Illnesses: An Evaluation of CrowdMed

http://www.jmir.org/2016/1/e12/

 

1Houston Veterans Affairs Center for Innovations in Quality, Effectiveness and Safety, Health Services Research and Development, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, United States

2Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX, United States

3Department of Biomedical Informatics, University of California San Diego, La Jolla, CA, United States

Corresponding Author:

Hardeep Singh, MD, MPH

 

Houston Veterans Affairs Center for Innovations in Quality, Effectiveness and Safety

Michael E. DeBakey Veterans Affairs Medical Center

VA HSR&D Center of Innovation (152)

2002 Holcombe Boulevard

Houston, TX, 77030

United States

Phone: 1 713 794 8601

Fax:1 713 748 7359

Email: hardeeps [at] bcm.edu

ABSTRACT

Background: Despite visits to multiple physicians, many patients remain undiagnosed. A new online program, CrowdMed, aims to leverage the “wisdom of the crowd” by giving patients an opportunity to submit their cases and interact with case solvers to obtain diagnostic possibilities.

Objective: To describe CrowdMed and provide an independent assessment of its impact.

Methods: Patients submit their cases online to CrowdMed and case solvers sign up to help diagnose patients. Case solvers attempt to solve patients’ diagnostic dilemmas and often have an interactive online discussion with patients, including an exchange of additional diagnostic details. At the end, patients receive detailed reports containing diagnostic suggestions to discuss with their physicians and fill out surveys about their outcomes. We independently analyzed data collected from cases between May 2013 and April 2015 to determine patient and case solver characteristics and case outcomes.

Results: During the study period, 397 cases were completed. These patients previously visited a median of 5 physicians, incurred a median of US $10,000 in medical expenses, spent a median of 50 hours researching their illnesses online, and had symptoms for a median of 2.6 years. During this period, 357 active case solvers participated, of which 37.9% (132/348) were male and 58.3% (208/357) worked or studied in the medical industry. About half (50.9%, 202/397) of patients were likely to recommend CrowdMed to a friend, 59.6% (233/391) reported that the process gave insights that led them closer to the correct diagnoses, 57% (52/92) reported estimated decreases in medical expenses, and 38% (29/77) reported estimated improvement in school or work productivity.

Conclusions: Some patients with undiagnosed illnesses reported receiving helpful guidance from crowdsourcing their diagnoses during their difficult diagnostic journeys. However, further development and use of crowdsourcing methods to facilitate diagnosis requires long-term evaluation as well as validation to account for patients’ ultimate correct diagnoses.

J Med Internet Res 2016;18(1):e12

doi:10.2196/jmir.4887

KEYWORDS

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Risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy

Posted on January 15, 2016 by Maurice Preter MD

The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: A systematic review and meta-analysis

 

 

http://onlinelibrary.wiley.com/doi/10.1111/bcp.12849/abstract

  1. Anick Bérard1,2,*,
  2. Noha Iessa1,2,
  3. Sonia Chaabane1,2,
  4. Flory T. Muanda1,2,
  5. Takoua Boukhris1,2 and
  6. Jin-Ping Zhao1,2

DOI: 10.1111/bcp.12849

Article has an altmetric score of 190

Additional Information(Show All)

Author InformationPublication History

  1. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bcp.12849.

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Keywords:

  • Paroxetine;
  • pregnancy;
  • major malformations;
  • cardiac malformations;
  • meta-analysis

Aims

The aim of this study was to perform an up-to-date meta-analysis on the risk of cardiac malformations associated with gestational exposure to paroxetine, taking into account indication, study design, and reference category.

Method

A systematic review of studies published between 1966 and November 2015 was conducted using EMBASE and MEDLINE. Studies reporting major malformations with first trimester exposure to paroxetine were included. Potentially relevant articles were assessed and relevant data extracted to calculate risk estimates. Outcomes included any major malformations, and major cardiac malformations. Pooled odds ratios and 95% confidence intervals were calculated using random-effects models.

Results

Twenty-three studies were included. Compared to non-exposure to paroxetine, first trimester use of paroxetine was associated with an increased risk of any major congenital malformations combined (pooled OR 1.23, 95% CI 1.10, 1.38; n=15 studies); major cardiac malformations (pooled OR 1.28, 95% CI 1.11, 1.47; n=18 studies), specifically bulbus cordis anomalies and anomalies of cardiac septal closure (pooled OR 1.42, 95% CI 1.07, 1.89; n=8 studies), atrial septal defects (pooled OR 2.38, 95% CI 1.14, 4.97; n=4 studies), and right ventricular outflow track defect (pooled OR 2.29, 95% CI 1.06, 4.93; n=4 studies). Although the estimates varied depending on the comparator group, study design and malformation detection period, a trend towards increased risk was observed.

Conclusions

Paroxetine use during the first trimester of pregnancy is associated with an increased risk of any major congenital malformations and cardiac malformations. The increase in risk is not dependent on the study method or population.

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Stress resilience and subsequent risk of type 2 diabetes in 1.5 million young men

Posted on January 15, 2016 by Maurice Preter MD

 

 

http://link.springer.com/article/10.1007/s00125-015-3846-7

  • Casey Crump 
  • , Jan Sundquist
  • , Marilyn A. Winkleby
  • , Kristina Sundquist

$39.95 / €34.95 / £29.95 *

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Abstract

Aims/hypothesis

Psychosocial stress in adulthood is associated with a higher risk of type 2 diabetes, possibly mediated by behavioural and physiological factors. However, it is unknown whether low stress resilience earlier in life is related to subsequent development of type 2 diabetes. We examined whether low stress resilience in late adolescence is associated with an increased risk of type 2 diabetes in adulthood.

Methods

We conducted a national cohort study of all 1,534,425 military conscripts in Sweden during 1969–1997 (97–98% of all 18-year-old men nationwide each year) without prior diagnosis of diabetes, who underwent standardised psychological assessment for stress resilience (on a scale of 1–9) and were followed up for type 2 diabetes identified from outpatient and inpatient diagnoses during 1987–2012 (maximum attained age 62 years).

Results

There were 34,008 men diagnosed with type 2 diabetes in 39.4 million person-years of follow-up. Low stress resilience was associated with an increased risk of developing type 2 diabetes after adjusting for BMI, family history of diabetes, and individual and neighbourhood socioeconomic factors (HR for lowest vs highest quintile: 1.51; 95% CI 1.46, 1.57; p < 0.0001), including a strong linear trend across the full range of stress resilience (p trend < 0.0001). This association did not vary by BMI level, family history of diabetes or socioeconomic factors.

Conclusions/interpretation

These findings suggest that low stress resilience may play an important long-term role in aetiological pathways for type 2 diabetes. Further elucidation of the underlying causal factors may help inform more effective preventive interventions across the lifespan.

Keywords

Psychological resilience Psychological stress Type 2 diabetes mellitus

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