Ketogenic Diet vs Mixed Diet for Heart Failure

Overseen by Yuchi Han, MD, MMSc

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Ohio State University

Disqualifiers: Pregnancy, Type I diabetes, Severe kidney disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is comparing a ketogenic diet and a low-fat diet in people with heart failure and diabetes or related conditions. The goal is to see which diet improves exercise tolerance better. The ketogenic diet helps the body use fat for energy, while the low-fat diet focuses on reducing fat intake.

Will I have to stop taking my current medications?

The trial requires that your current medications for heart failure and diabetes remain stable for at least 3 months before and during the study. However, changes in the dose of oral diuretics are allowed if they are stable for 1 week before starting the trial.

What data supports the effectiveness of the ketogenic diet treatment for heart failure?

Research suggests that low-carbohydrate diets, like the ketogenic diet, can improve heart function by reducing insulin resistance and improving blood sugar control, which may help people with heart failure. Additionally, these diets have been shown to aid in weight loss and improve cardiovascular risk factors, which can be beneficial for heart health. ^{1 2 3 4 5}

Is the ketogenic diet safe for humans?

Research shows that ketogenic diets, which are low in carbohydrates and high in fats, are generally safe for weight loss and can improve certain heart health markers like triglycerides and good cholesterol levels. However, more long-term studies are needed to fully understand their safety over extended periods. ^{2 4 6 7 8}

How does the ketogenic diet treatment for heart failure differ from other treatments?

The ketogenic diet is unique for heart failure treatment because it focuses on increasing ketone body metabolism, which provides an alternative energy source for the heart, potentially improving cardiac function. Unlike standard treatments, it involves a high-fat, low-carbohydrate diet that may enhance energy production in the failing heart. ^{9 10 11 12 13}

Research Team

Yuchi Han, MD, MMSc

Principal Investigator

Ohio State University

Eligibility Criteria

Adults aged 18-80 with heart failure, normal heart pumping function, and either diabetes, pre-diabetes, metabolic syndrome or obesity (BMI between 25-50) can join. They must have stable health for the past 3 months and be able to exercise on a treadmill. People with severe kidney disease, Type I diabetes, recent heart attacks or certain other serious health conditions cannot participate.

Inclusion Criteria

My heart and diabetes medications have been stable for the last 3 months.

My BMI is between 25 and 50, or I have Type 2 Diabetes, prediabetes, or metabolic syndrome.

Your heart function tests show certain abnormalities related to the pressure in your lungs and blood vessels.

Exclusion Criteria

I am not pregnant, breastfeeding, nor plan to become pregnant during the study.

I have not had a heart attack or severe heart issue in the last 30 days.

My kidney function is severely reduced.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Baseline Monitoring

Participants apply a sensor one week prior to starting the study to capture baseline metabolic status

1 week

1 visit (in-person)

Initial Diet Intervention

Participants follow a specified diet with provided food and dietary coaching

6 weeks

Weekly visits (in-person or virtual)

Free-living Diet Period

Participants continue the diet with educational materials and coaching, without provided food

20-22 weeks

Frequent coaching sessions (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Ketogenic Diet (Behavioural Intervention)
• Mixed Diet (Behavioural Intervention)

Trial Overview The trial is testing how well two diets - a low carbohydrate ketogenic diet and a low-fat mixed diet - help people with heart failure improve their ability to exercise. Participants will be randomly assigned to one of these diets to see which is more effective.

Participant Groups

Group I: Low-fat mixed Diet Experimental Treatment 1 Intervention

This arm will be provided food consisting of \~25% fat, and the remaining calories from carbohydrate (\~55% after accounting for protein at \~20%).

Group II: Ketogenic Diet Experimental Treatment 1 Intervention

This arm will be provided food to induce a state of nutritional ketosis in each person as defined as blood Beta-hydroxybutyrate (3-OHB) ≥0.5 millimoles (mM), which will require most participants to consume \<50 g/day carbohydrate and 1.5g/kg reference weight protein. Fat will comprise the remaining calories with an emphasis on monounsaturated and saturated sources from whole foods.

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

Dr. John J. Warner

Ohio State University

Chief Executive Officer since 2023

MD, MBA

Dr. Peter Mohler

Ohio State University

Chief Medical Officer since 2023

PhD in Molecular Biology

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Pete Hegseth

United States Department of Defense

Chief Executive Officer

Bachelor's degree in Political Science from Princeton University, JD from Harvard Law School

Lisa Hershman

United States Department of Defense

Chief Medical Officer since 2021

MD from Uniformed Services University of the Health Sciences

Findings from Research

In patients with diabetic cardiomyopathy (DMCM), low carbohydrate (LC) diets may improve glycemic control and reduce insulin resistance, potentially leading to better heart function and reduced medication needs.

Traditional low fat (LF) diets, which are higher in carbohydrates, could worsen insulin resistance and glycemic control in DMCM patients, suggesting that LC diets may be a safer and more effective dietary approach for managing heart failure in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Carbohydrate Diets for Diabetic Cardiomyopathy: A Hypothesis. Kleissl-Muir, S., Rasmussen, B., Owen, A., et al.[2023]

Low-carbohydrate/high-protein diets were found to be more effective than low-fat/high-carbohydrate diets for weight loss and improving cardiovascular risk factors, based on a systematic review of 13 randomized controlled trials lasting at least 6 months.

Participants showed a preference for low-carbohydrate diets, as indicated by a higher dropout rate in the low-fat diet group, suggesting that these diets may be more sustainable for long-term weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities. Hession, M., Rolland, C., Kulkarni, U., et al.[2022]

Individuals on a very-low-carbohydrate ketogenic diet (VLCKD) experienced greater long-term weight loss compared to those on a conventional low-fat diet (LFD), with a mean difference of -0.91 kg across 13 studies involving 1415 patients.

The VLCKD also led to improvements in cardiovascular risk factors, including lower triglycerides and diastolic blood pressure, as well as increased HDL cholesterol, suggesting it may be a beneficial approach for managing obesity and related health risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Bueno, NB., de Melo, IS., de Oliveira, SL., et al.[2022]

A meta-analysis of 11 randomized controlled trials involving 1369 participants found that low-carbohydrate (LC) diets led to greater weight loss compared to low-fat (LF) diets, with an average reduction of 2.17 kg.

While LC diets improved weight loss and increased HDL-cholesterol, they also resulted in a rise in LDL-cholesterol, indicating that the benefits of LC diets must be balanced against potential cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors: a meta-analysis of randomised controlled trials. Mansoor, N., Vinknes, KJ., Veierød, MB., et al.[2022]

In a 12-month clinical trial with 148 adults, a low-carbohydrate diet led to greater weight loss and improved body composition compared to a low-fat diet, despite similar adherence levels between the two groups.

Better adherence to the low-carbohydrate diet was linked to significant weight loss (2.2 kg) and increased lean mass, while adherence to the low-fat diet did not result in any changes in weight or body composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to low-carbohydrate and low-fat diets in relation to weight loss and cardiovascular risk factors. Hu, T., Yao, L., Reynolds, K., et al.[2021]

The Modified Atkins Diet (MAD) significantly improved seizure control in patients with intractable epilepsy, reducing daily seizure frequency from an average of 13.29 to 2.71 over nine months.

Mothers of the patients also experienced a significant improvement in their quality of life across all domains measured, indicating that MAD not only benefits the patients but also positively impacts their caregivers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with MAD on children with epilepsy in Egypt after classic KD failure. El Rashidy, OF., Nassar, MF., El Gendy, YG., et al.[2018]

In a year-long study involving 118 participants with abdominal obesity, both a very-low-carbohydrate, high-saturated-fat diet (LC) and a high-carbohydrate, low-fat diet (LF) resulted in similar weight loss and body composition changes, indicating that both diets can be effective for weight management under controlled energy conditions.

The LC diet showed additional cardiometabolic benefits, including greater reductions in triglycerides and increases in HDL cholesterol compared to the LF diet, although it also led to a significant increase in LDL cholesterol, which should be monitored in individuals following this diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo. Brinkworth, GD., Noakes, M., Buckley, JD., et al.[2023]

Ketogenic diets, which are low in carbohydrates and high in fats, have been shown to be effective for weight loss and can improve triglyceride and HDL cholesterol levels compared to low-fat diets.

Despite concerns about their high fat content, the degree of carbohydrate restriction needed to achieve ketosis is still unclear, indicating a need for more standardized research on these diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diets for weight loss: A review of their principles, safety and efficacy. Sumithran, P., Proietto, J.[2022]

Regulating ketone body metabolism may offer a new therapeutic strategy for heart failure (HF), as recent studies indicate that the failing heart increasingly relies on ketone bodies for energy due to decreased utilization of fatty acids and glucose.

Enhancing ketone body metabolism in HF appears to be a compensatory mechanism that can improve cardiac function, suggesting that ketogenic therapy could be beneficial in treating patients with heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Potential implications of ketone body metabolism changes and ketogenic therapy in the treatment of heart failure]. Wang, Q., Yan, S., Kuang, S., et al.[2023]

The ketogenic diet (KD) can improve glycemic control and support sustained weight loss, making it a potential intervention for type 2 diabetes and obesity, while also offering beneficial cardiovascular effects through improved cardiac energetics.

However, the KD may lead to adverse effects such as increased triglycerides and LDL cholesterol levels, which could counteract its cardiovascular benefits, along with challenges in diet adherence and uncertainty about long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic Diet and Cardiac Substrate Metabolism. Luong, TV., Abild, CB., Bangshaab, M., et al.[2022]

In heart failure, the heart struggles to produce enough energy due to decreased mitochondrial metabolism, but ketone bodies can serve as an alternative energy source, potentially improving heart function.

While ketogenic diets alone have shown limited benefits for heart function, intravenous ketone infusions and ketone ester cocktails may enhance cardiac performance, suggesting that boosting ketone oxidation could be a promising treatment strategy for heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketone metabolism in the failing heart. Lopaschuk, GD., Karwi, QG., Ho, KL., et al.[2021]

In a study involving 11 healthy, normal-weight participants, a high-fat ketogenic diet (KD) did not improve cognitive function, mood, or sleep quality compared to a high-carbohydrate, low-fat diet over a 3-week period.

Despite achieving nutritional ketosis, the KD showed no significant effects on tasks measuring vigilance, memory, or executive function, indicating that this diet may not enhance cognitive performance in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three consecutive weeks of nutritional ketosis has no effect on cognitive function, sleep, and mood compared with a high-carbohydrate, low-fat diet in healthy individuals: a randomized, crossover, controlled trial. Iacovides, S., Goble, D., Paterson, B., et al.[2023]

In a study of 28 overweight and obese adults, both ketogenic diets (KDs) and low-fat diets (LFD) resulted in similar weight loss after 6 weeks, averaging around 6-8 kg, indicating that KDs can be effective for weight management.

The KD groups experienced a significant increase in aldosterone levels (88% in the placebo group and 144% in the ketone salt group), but this did not negatively impact blood pressure or other cardiovascular risk factors, suggesting that KDs may be safe in terms of cardiometabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Hypocaloric Low-Fat, Ketogenic, and Ketogenic and Ketone Supplement Diets on Aldosterone and Renin. Belany, P., Kackley, ML., Zhao, S., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Low Carbohydrate Diets for Diabetic Cardiomyopathy: A Hypothesis. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. [2022]

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Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors: a meta-analysis of randomised controlled trials. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Adherence to low-carbohydrate and low-fat diets in relation to weight loss and cardiovascular risk factors. [2021]

6. Denmark pubmed.ncbi.nlm.nih.gov

Experience with MAD on children with epilepsy in Egypt after classic KD failure. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Ketogenic diets for weight loss: A review of their principles, safety and efficacy. [2022]

9. China pubmed.ncbi.nlm.nih.gov

[Potential implications of ketone body metabolism changes and ketogenic therapy in the treatment of heart failure]. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Ketogenic Diet and Cardiac Substrate Metabolism. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Ketone metabolism in the failing heart. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Three consecutive weeks of nutritional ketosis has no effect on cognitive function, sleep, and mood compared with a high-carbohydrate, low-fat diet in healthy individuals: a randomized, crossover, controlled trial. [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Effects of Hypocaloric Low-Fat, Ketogenic, and Ketogenic and Ketone Supplement Diets on Aldosterone and Renin. [2023]