Ketogenic Diet for Cardiovascular Health

Overseen By Stacey Meily

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Penn State University

Must not be taking: Antihypertensives, Statins, Antidiabetics, Steroids

Disqualifiers: Diabetes, Liver disease, Cardiovascular event, others

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

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this clinical trial is to examine the effect of the ketogenic diet over four weeks on blood lipid levels and risk factors for heart disease in adults with a healthy BMI compared to adults with a body mass index (BMI) in the range for obesity. The main questions it aims to answer are: * Does the ketogenic diet cause larger increases in "bad cholesterol" (low density lipoprotein-cholesterol) in adults with a healthy BMI compared to adults with BMI in the range for obesity? * Does the ketogenic diet cause larger decreases in vascular health in adults with a healthy BMI compared to adults with BMI in the range for obesity? Participants will: * Consume all of the study food provided and avoid intake of non-study foods during the 28-day diet period * Visit the metabolic kitchen daily (Monday-Friday) to pick up meals * Attend 5 fasting visits at the Clinical Research Center for testing

Will I have to stop taking my current medications?

The trial requires that participants do not take anti-hypertensive, lipid-lowering, or glucose-lowering drugs. If you take supplements that affect the study's outcomes, you must be willing to stop them during the study period.

Is the ketogenic diet safe for cardiovascular health?

The ketogenic diet may raise concerns for cardiovascular health, as some studies report cases of heart issues like type 2 myocardial infarction and significant increases in cholesterol levels. Monitoring heart health and cholesterol is advised for those on this diet. ^{1 2 3 4 5}

How does the ketogenic diet treatment for cardiovascular health differ from other treatments?

The ketogenic diet is unique because it focuses on high fat and low carbohydrate intake, which can improve heart health by enhancing cardiac energy use and reducing oxygen needs. Unlike traditional low-fat diets, it may also lead to better weight loss and cardiovascular risk reduction, although it can raise cholesterol levels and requires careful adherence. ^{2 5 6 7 8}

What data supports the effectiveness of the treatment Ketogenic Diet for cardiovascular health?

Research shows that low-carbohydrate diets, like the ketogenic diet, can lead to weight loss and improve some heart health markers, such as cholesterol and blood pressure, more effectively than low-fat diets. However, there are concerns about potential increases in cholesterol levels, so monitoring is important. ^{2 3 9 10 11}

Are You a Good Fit for This Trial?

This trial is for healthy adults who are either at a normal weight or have obesity, as determined by their BMI. They must be willing to follow a strict ketogenic diet provided by the study for four weeks and can commit to daily visits on weekdays to pick up meals and attend five fasting tests.

Inclusion Criteria

Fasting triglycerides <350 mg/dL

Fasting direct LDL-C ≤100 mg/dL

Fasting blood glucose <126 mg/dL

Exclusion Criteria

I have taken oral steroids in the last month.

I have had weight loss surgery in the past.

Principal Investigator discretion related to the potential participant's ability to adhere to the study requirements including being able to come to the metabolic kitchen to pick-up food five days per week

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow a ketogenic diet for 28 days, with daily meal pickups and fasting visits for testing

4 weeks

5 fasting visits (in-person), daily meal pickups (Monday-Friday)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic Diet

Trial Overview The study is testing how a ketogenic diet affects blood lipid levels and heart disease risk factors over four weeks in two groups of adults: those with a normal BMI versus those with an obese BMI. It aims to see if there's a difference in 'bad cholesterol' increase or vascular health decrease between these groups.

How Is the Trial Designed?

Group I: Low BMI Experimental Treatment 1 Intervention

BMI 18.5 - 22 kg/m\^2 Intervention: Ketogenic diet 28 days

Group II: High BMI Active Control 1 Intervention

BMI 30-35 kg/m\^2 Intervention: Ketogenic diet 28 days

Who Is Running the Clinical Trial?

Penn State University

Lead Sponsor

Trials

380

Recruited

131,000+

Published Research Related to This Trial

The Mediterranean diet is strongly supported by evidence showing significant reductions in mortality rates and heart attack occurrences, making it a highly recommended option for patients aiming to reduce cardiovascular disease risk.

While popular diets like Atkins and South Beach are effective for weight loss, they lack substantial evidence for long-term health benefits, highlighting the importance of focusing on patient-oriented outcomes in dietary counseling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diets for cardiovascular disease prevention: what is the evidence? Walker, C., Reamy, BV.[2022]

The ketogenic diet (KD) can lead to significant increases in total cholesterol and low-density lipoprotein (LDL) cholesterol, especially in lean individuals, highlighting the need for careful lipid monitoring during the diet.

Improvements in cholesterol levels were observed after discontinuing the KD, suggesting that while the diet may aid in weight loss and glycemic control, it can have adverse effects on lipid profiles that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profound Elevation in LDL Cholesterol Level Following a Ketogenic Diet: A Case Series. Crosier, R., McPherson, R.[2022]

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 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]

Replacing saturated fatty acids (SAFA) with unsaturated fatty acids can improve blood lipid profiles and lower the risk of coronary heart disease (CHD), highlighting the importance of dietary fat composition in cardiovascular health.

Regular consumption of fatty fish, which are high in omega-3 fatty acids, is linked to reduced risks of fatal CHD and stroke, supporting dietary guidelines that recommend limiting SAFA and increasing intake of healthy fats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progressing Insights into the Role of Dietary Fats in the Prevention of Cardiovascular Disease. Zock, PL., Blom, WA., Nettleton, JA., et al.[2022]

A 38-year-old male developed type II myocardial infarction after starting a very-low-carbohydrate ketogenic diet (VLC-KD) just 4 weeks prior, raising concerns about the diet's cardiovascular safety.

Despite normal coronary arteries, the patient exhibited significant cardiac stress indicators, including elevated troponins and ST-T changes on ECG, suggesting a potential link between VLC-KD and cardiac events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type 2 Myocardial Infarction Related to Very Low Carbohydrate Ketogenic Diet. Taha, A., Ahmed, S., Ahmed Mbbs, R., et al.[2022]

A 21-day very low-calorie ketogenic diet (VLCKD) resulted in significant weight loss and improvements in insulin resistance without negatively impacting overall nutritional status or causing adverse changes in liver and kidney function.

Both VLCKD1 and VLCKD2 led to similar reductions in body mass index and fat mass, but also resulted in increased levels of uric acid and creatinine, indicating the need for monitoring these parameters during such diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of very-low-calorie ketogenic diet: a double blind randomized crossover study. Colica, C., Merra, G., Gasbarrini, A., et al.[2022]

The ketogenic diet (KD) is effective in controlling drug-refractory seizures in children and adolescents, but it is associated with recurrent dyslipidemia, particularly hypercholesterolemia, which can negatively impact lipid profiles.

While KD has clear benefits for seizure control, it may increase cardiometabolic risk due to structural changes in low-density lipoprotein (LDL) particles, suggesting a need for further investigation into lipid and oxidative metabolism in patients on this diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet in epileptic children: impact on lipoproteins and oxidative stress. Lima, PA., de Brito Sampaio, LP., Damasceno, NR.[2017]

In a study of 26 children after one year and 13 children after two years on a ketogenic diet, initial increases in LDL cholesterol and apolipoprotein B were observed, but these changes were not significant after 24 months, suggesting potential reversibility.

Carotid artery function showed a gradual decrease in distensibility during the first year, but no significant long-term changes in carotid intima-media thickness or inflammatory markers were found after two years, indicating that the diet may not have lasting adverse effects on vascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ketogenic diet on vascular function. Kapetanakis, M., Liuba, P., Odermarsky, M., et al.[2017]

Low-carbohydrate ketogenic diets significantly improved cardiovascular risk factors in overweight or obese patients, particularly those with type 2 diabetes, leading to lower fasting plasma glucose and hemoglobin A1c levels.

These diets also resulted in notable reductions in body mass index, weight, and waist circumference, while improving lipid profiles by lowering triglycerides and potentially increasing high-density lipoprotein levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low carbohydrate ketogenic diets reduce cardiovascular risk factor levels in obese or overweight patients with T2DM: A meta-analysis of randomized controlled trials. Luo, W., Zhang, J., Xu, D., 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]

Citations

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

Diets for cardiovascular disease prevention: what is the evidence? [2022]

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

Profound Elevation in LDL Cholesterol Level Following a Ketogenic Diet: A Case Series. [2022]

3. 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]

4. 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]

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

Progressing Insights into the Role of Dietary Fats in the Prevention of Cardiovascular Disease. [2022]

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

Type 2 Myocardial Infarction Related to Very Low Carbohydrate Ketogenic Diet. [2022]

7. Italy pubmed.ncbi.nlm.nih.gov

Efficacy and safety of very-low-calorie ketogenic diet: a double blind randomized crossover study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Ketogenic diet in epileptic children: impact on lipoproteins and oxidative stress. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Effects of ketogenic diet on vascular function. [2017]

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

Low carbohydrate ketogenic diets reduce cardiovascular risk factor levels in obese or overweight patients with T2DM: A meta-analysis of randomized controlled trials. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Ketogenic Diet and Cardiac Substrate Metabolism. [2022]