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Can a Ketogenic Diet Reverse Heart Failure?

It should be tested whether high fat or ketogenic diets can improve heart failure from typical etiologies such as myocardial infarction and chronic hypertension

WeightControl.com Interview with:
Kyle S. McCommis, Ph.D.
Assistant Professor
Biochemistry & Molecular Biology
St. Louis University School of Medicine

WeightControl.com: What is the background for this study? What are the main findings?

Response: It is well established that the heart is normally very flexible in what substrates it can metabolize in order to quickly adapt to different physiological scenarios. However, in cardiomyopathies such as heart failure, this metabolic flexibility is lost and there is a decreased ability for the heart to perform oxidative metabolism. This has previously been attributed mainly to a decrease in fat oxidation by the heart, but some studies also indicate decreased glucose oxidation.

We therefore were interested to see if the mitochondrial pyruvate carrier (MPC), which transports pyruvate derived from glucose or lactate into the mitochondria, could be playing a role in heart failure.

We first identified lower expression of the MPC proteins in failing human hearts compared to non-failing control hearts. We then created a MPC2 knockout mouse, which spontaneously developed heart failure with age. These failing hearts of course could not metabolize pyruvate, but they also displayed lower expression of fat oxidation enzymes.

We hypothesized that the hearts may be improved if we provided the mice with a diet that provided nutrients the hearts were better able to use. When we switched the diet to a low carbohydrate, high fat “ketogenic” diet, these MPC2 knockout mice no longer showed any signs of heart failure. We also aged some mice to where they developed severe heart failure, then switched them to the ketogenic diet, and shockingly observed almost complete reversal of their cardiac dysfunction. This lead us to question how the diet was rescuing these hearts; was it due to improved ketone body metabolism by the hearts, or due to improved fat metabolism from the large amount of dietary fat.

Essentially all of our experiments suggested that these failing hearts we regaining the ability to oxidize fatty acids, and were actually shutting off ketone body metabolism. Feeding the mice a normal “high fat” diet which contains enough carbohydrate and protein to not be overly ketogenic, was also able to prevent the heart failure in these mice.

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Weight Loss in Low Income Patients in Primary Care Settings

Clinically significant weight loss is possible in underserved, low-income patients in primary care settings.

WeightControl.com Interview with:
Peter Katzmarzyk, Ph.D., FACSM, FAHA, FTOS
Professor and Marie Edana Corcoran Endowed Chair
Pediatric Obesity and Diabetes
Assoc Exec Dir for Population and Public Health Sciences
Pennington Biomedical Research Center
Baton Rouge, LA

WeightControl.com: What is the background for this study?

Response: Obesity remains one of the greatest public health threats, and there is good evidence that intensive lifestyle interventions should be a primary approach to obesity management and treatment. However, there has been minimal uptake of obesity treatment approaches in primary care, which is the cornerstone of medicine in the US.

WeightControl.com: What are the main findings?

Response: We developed an intervention to reduce calorie intake and increase physical activity that was delivered by health coaches embedded in primary care clinics. The sample was diverse with a large percentage of low-income and African American patients. The results demonstrated that patients in the intensive lifestyle intervention lost approximately 5% of their initial body weight, compared to patients in usual care who lost about 0.5% of their body weight. These weight loss differences between the two groups were maintained out to 2 years, which demonstrates the durability of the intervention.

COVID-19 Linked to Difficulty with Weight Control

With the current concerns that the pandemic may lead to increases in obesity rates, it’s important to develop appropriate and large-scale support options for those aiming to manage their weight.

WeightControl.com Interview with:

Dr Sarah-Elizabeth Bennett
Senior Research Associate
Slimming World, UK

WeightControl.com: What is the background for this study?

Response: This research is part of a larger Health and Wellbeing study, investigating the behaviour changes made by members of Slimming World, the UK’s largest group-based weight management organisation. New members were surveyed regularly over the course of one year and a representative sample of non-members were also surveyed at similar timepoints for comparison. The survey at the six-month point coincided with lockdown, so questions were added to learn more about how lockdown measures had impacted the nation’s health, wellbeing, and lifestyle behaviours. The following findings were based on the responses of 222 members who had completed all 3 surveys to-date and 637 non-members.

Benefits of Weight Loss on Physical Function in Older Adults Differ by Sex and Race

We report greater weight loss-associated improvement in short physical performance battery score in women (versus men) and greater gait speed improvement in blacks (versus whites).

WeightControl.com Interview with:
Kristen M. Beavers, PhD, MPH, RD
Associate Professor
Department of Health and Exercise Science
Wake Forest University

WeightControl.com: What is the background for this study? What are the main findings?

Response: Consideration of differential treatment effects among subgroups in clinical trial research is a topic of increasing interest. This is an especially salient issue for weight loss trials, as most are over-represented by white women. The question we sought to address is: “Does sex or race moderate the effect of a weight loss intervention on physical function among older adults?”

In this pooled analysis of 1317 individuals participating in eight randomized clinical trials of weight loss — of which 30% were male and 21% were black — we report greater weight loss-associated improvement in short physical performance battery score in women (versus men) and greater gait speed improvement in blacks (versus whites).

How Much Fasting Is Necessary to Lose Weight?

The main findings of this study were a 3% weight loss in 8 weeks in both groups with a 550-calorie restriction (unintentional) and good adherence to both diets.

MedicalResearch.com Interview with:
Sofia Cienfuegos
PhD Candidate, Human Nutrition.
Department of Kinesiology and Nutrition
University of Illinois at Chicago

MedicalResearch.com: What is the background for this study?

Response: Intermittent fasting has been gaining a lot of popularity lately mainly due to a large group of the general population that don’t like to keep tabs on their caloric intake. Intermittent fasting is a safe and effective alternative to weight loss that does not require people consciously restricting calories. Time restricted feeding (TRF) is one specific type of IF that has been gaining a lot of popularity and public interest lately. Previous studies in TRF with the 16/8 method made people want to try and follow this diet strategy achieving promising results. Some people were wondering if shortening the feeding window even further would induce better results in terms of weight loss and cardiometabolic health.

Based on this question, we decided to test two different short time restricted feeding methods (18/6 and 20/4) to see if they could induce even better results in weight and health outcomes. We were also wondering if people were able to stick to these interventions considering the short eating window.

MedicalResearch.com: What are the main findings?

Response: The main findings of this study were a 3% weight loss in 8 weeks in both groups with a 550-calorie restriction (unintentional) and good adherence to both diets. Also, we found significant reductions in insulin resistance and oxidative stress in both intervention groups.

Scientists Explain Why Artificial Sweeteners Don’t Quench Our Appetite for Sugar

We identified a key gut-to-brain circuit responsible for our unquenchable sugar appetite.

WeightControl.com Interview with:
Alexander Sisti, MD/PhD Candidate
Zuker Lab
Columbia University

WeightControl.com: What is the background for this study?

Response: Our lab has studied the biology of mammalian taste for over two decades. Previous work has identified the receptors for all five basic taste qualities (sweet, sour, bitter, salty, umami).

In the course of these studies, we generated mice lacking sweet receptors (i.e. “sweet-blind”). Unexpectedly, we observed that these animals could eventually learn to identify and develop a preference for a sugar-containing bottle—even though they could not taste it. This was not true for artificial sweeteners. This led us to hypothesize that there was something about the sugar that made the animals feel good and want more of it.

We set out to identify the brain circuits underlying our insatiable appetite for sugar which could operate independently from the taste system. So, we searched the brain for areas activated by sugar but not artificial sweeteners and areas that responded to sugar in the sweet-blind animals. We wanted to identify where the sugar signal was coming from.

WeightControl.com: What are the main findings?

Response: Our work revealed that sugar activates a selective circuit from the gut to the brain. This pathway is responsible for our “wanting” of sugar. It does not respond to artificial sweeteners and operates completely independently from the classical tongue-to-brain taste system (which mediates “liking” of all sweet substances, including artificial sweeteners). The discovery of this new circuit fundamentally changes the way we think about the action of sugar in the brain.

WeightControl.com: What should readers take away from your report?

Response: Our most significant findings are:

We identified a key gut-to-brain circuit responsible for our unquenchable sugar appetite.
We demonstrate that silencing this circuit is able to completely abolish development of sugar preference. Essentially, we were able to create “sugar-blind” animals insensitive to sugar craving. Given the extraordinary impact of sugar on the global epidemic of obesity, metabolic syndrome and diabetes, identifying new strategies to curb sugar consumption could have a meaningful impact on human health.
Our results explain why artificial sweeteners have failed in reducing our appetite for sugar, as they cannot activate this gut-brain circuit.

Citation:

Hwei-Ee Tan, Alexander C. Sisti, Hao Jin, Martin Vignovich, Miguel Villavicencio, Katherine S. Tsang, Yossef Goffer, Charles S. Zuker. The gut–brain axis mediates sugar preference. Nature, 2020; DOI: 10.1038/s41586-020-2199-7

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Weight Control: Better to Eat a Big Breakfast than Big Dinner

The importance of the time of day and our internal clock for food intake and energy metabolism is a very exciting research field. Future studies should investigate why we spend so much more energy after breakfast than after dinner

WeightControl.com Interview with:
M. Sc. Juliane Richter
University of Lübeck
Center of Brain, Behavior and Metabolism
Section of Psychoneurobiology

WeightControl.com: What is the background for this study? What are the main findings?

Response: The background for this study is that there is still the misbelief that it does not matter when we eat and that the only thing that counts is the energy balance of the whole day. However, since our body has an internal clock and many processes in the body, for example glucose metabolism, are subject to diurnal variations, we investigated whether diet-induced thermogenesis also varies during the course of the day.

Diet-induced thermogenesis is the energy our body spends for the digestion, absorption and transport of nutrients. We found that diet-induced thermogenesis after breakfast is more than twice as high as after dinner. We also investigated whether this difference in time of day depends on the amount of calories consumed. In both cases, high- and low-calorie meals, the body spends more energy after breakfast than after dinner.

breakfast-timing of meals for weight control

Obesity Prevented and Reversed in Mice By Blocking Cellular Receptor

We are beginning to understand how the blockage of the AHR prevents and reverses obesity, which may lead to a therapeutic treatment of obesity in humans.

WeightControl.com Interview with:
Craig R. Tomlinson, Ph.D.
Director of Genomics & Molecular Biology Shared Resource
Norris Cotton Cancer Center
Geisel School of Medicine at Dartmouth
Dartmouth Hitchcock Medical Center
Lebanon, NH 03756

WeightControl.com: What is the background for this study?

Response: Obesity, a global epidemic, is a known contributor to numerous diseases, including diabetes, heart disease, and cancer. Preventing and reversing the obesity epidemic would be a critical aid in preventing and treating these diseases.

Our laboratory had discovered that a drug called NF, which was known to block the activity of a cellular receptor called the AHR, prevented obesity in mice fed a high-fat diet. We undertook studies to determine how the AHR, when inhibited by NF, exerted its effects on obesity.

Is There a Link Between Obesity and Periodontal Disease?

Clinicians should educate patients about the importance of weight control affecting oral/periodontal health.

WeightControl.com Interview with:

Andres Pinto DMD, MPH, MSCE, MBA, FDS RCSEd, FICD
Professor and Chair
Oral and Maxillofacial Medicine and Diagnostic Sciences
Director, Oral Medicine Internship and MSD Program

University Hospitals Cleveland Medical Center
Assistant Dean for Graduate Studies
Case Western Reserve University and
Cleveland Clinic
Health Education Campus
School of Dental Medicine
Cleveland, OH

WeightControl.com: What is the background for this study? What are the main findings?

Response: There is strong association between oral health and systemic health. Periodontal disease affects almost half of Americans and is characterized by increased inflammation. The focus of our review was to evaluate the association between obesity and periodontal disease, which has been reported earlier, with attention to the effects on the non-surgical management of periodontal disease. Our results indicate both disorders share similar inflammatory characteristics and may be associated.

However, multiple factors mediate this relationship, of course including oral hygiene. We were unable to find conclusive evidence on the impact of obesity on treatment planning for periodontal therapy, although the presumptive common pathophysiology provides an opportunity for active patient education.

Using Diet Pills For Weight Control Linked to Increased Risk of Eating Disorder in Young Women

Over-the-counter diet pill and laxative use are not a healthy way to manage weight and young women, or consumers of any age or gender, should not use them for weight control

WeightControl.com Interview with:

Jordan A. Levinson BA
Division of Adolescent and Young Adult Medicine
Boston Children’s Hospital
Boston, MA

WeightControl.com: What is the background for this study?

Response: Many unhealthy weight control behaviors, including the use of diet pills and laxatives for weight control, can put individuals at risk for developing eating disorders. Though the use of these products is common, it is incredibly dangerous and not recommended by health care providers for weight control.