Ketogenic Diet vs Mixed Diet for Heart Failure

Overseen By Alyssa Marie Castillo, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ohio State University

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two different diets affect exercise tolerance in people with heart failure who also have diabetes, pre-diabetes, metabolic syndrome, or obesity. Participants will follow either a ketogenic diet, low in carbs, or a mixed diet, low in fat. The study aims to determine which diet improves exercise capacity for those with heart failure where the heart pumps normally. Individuals who have had heart failure for at least three months, are managing their condition with stable medication, and can participate in exercise treadmill testing might be suitable candidates. As an unphased trial, this study offers participants the chance to contribute to valuable research that could enhance dietary recommendations for heart failure patients.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the ketogenic diet, low in carbs and high in fats, can affect heart health. Some studies suggest this diet might lower heart disease risk. However, results vary, and outcomes depend on individual health and conditions.

For a mixed diet, which balances fats, carbs, and proteins, several studies highlight its potential to boost heart health. Diets like the Mediterranean diet, which are similar, have been linked to a lower risk of heart disease. This suggests that a balanced diet might be safe and beneficial for heart health.

Overall, both ketogenic and mixed diets have shown possible heart health benefits in different studies. However, individual responses vary, so personal health conditions should be considered when evaluating these diet options. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore how different diets might impact heart failure management, which is not typically addressed by dietary changes alone. The ketogenic diet is unique as it aims to induce a state of nutritional ketosis, potentially offering metabolic benefits like improved energy utilization in heart cells. Meanwhile, the low-fat mixed diet provides a balanced approach with a higher carbohydrate content, which may support heart health in a different way. Both dietary interventions offer a fresh perspective compared to conventional heart failure treatments, such as medications and lifestyle changes, by directly altering macronutrient intake to see if it can improve heart function.

What evidence suggests that this trial's treatments could be effective for heart failure?

This trial will compare the effects of a Ketogenic Diet and a Low-fat Mixed Diet on heart failure. Research has shown that low-carbohydrate ketogenic diets might lower the risk of heart failure. Some studies suggest these diets can reduce the chances of heart disease and sudden death, although results can vary. Meanwhile, low-fat diets have improved heart health, with evidence indicating they can help prevent major heart problems. Both diets may benefit heart health, but the best choice depends on individual needs and personal response to the diet. ^{1 3 6 7 8}

Who Is on the Research Team?

Yuchi Han, MD, MMSc

Principal Investigator

Ohio State University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic Diet
• Mixed Diet

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.

How Is the Trial Designed?

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+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

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 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]

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]

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 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]

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]

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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0146280624000410

Invited Review Article Ketogenic diet and cardiovascular risk Very low carbohydrate high-fat diet. Cardiovascular risk. Cardiovascular ... This aspect could also potentially impact the heart failure pharmacotherapy efficacy.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9792675/

Low carbohydrate ketogenic diets reduce cardiovascular ... ... disease, heart failure, and sudden death. Many individuals with ... Effects of calorie restricted low carbohydrate high fat ketogenic vs.

3. jacc.org jacc.org/doi/10.1016/j.jchf.2023.05.009

Ketogenic Diet in Heart Failure: Fact or Fiction?∗ A ketogenic diet high in animal-based saturated fats may increase levels of the metabolite TMAO and in turn promote atherosclerosis and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11368127/

The ketogenic diet does not improve cardiac function and ... However, studies demonstrating the efficacy of a ketogenic diet in lessening heart failure severity have produced mixed results. ... low-carbohydrate diet ...

5. nature.com nature.com/articles/s41598-024-73384-x

The ketogenic diet has the potential to decrease all-cause ... ... fats, which have been linked to a decreased risk of heart disease. ... The significant impact of high-fat, low-carbohydrate ketogenic diet ...

6. ahajournals.org ahajournals.org/doi/10.1161/circ.150.suppl_1.4139384

Abstract 4139384: Retrospective Review of the Safety and ... ... Low Carbohydrate Ketogenic Diet in Overweight or Obese Patients with Heart Failure ... No Low-Fat Diet for the Failing Heart? Heinrich Taegtmeyer ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10210275/

Effects of ketogenic diet on health outcomes: an umbrella ... The effect of a ketogenic low-carbohydrate, high-fat diet on aerobic ... cardiovascular disease: ketogenic diet, intermittent fasting, and ...

8. ahs.atlantichealth.org ahs.atlantichealth.org/about-us/stay-connected/news/content-central/2023/keto-diets-and-heart-health.html

Keto Diets and Heart Health: Harmful or Helpful? However, previous research has shown that a low carb, high fat (LCHF) ... ketogenic or keto-like diet and developing heart disease. “In ...