Low-Carb vs. Low-Fat Diets for Obesity

Overseen By Kevin Hall, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Must not be taking: Diet medications, Psychiatric medications

Disqualifiers: Diabetes, Cancer, Pregnancy, others

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

Compensation: Varies

Number of Visits: 5

100 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: In a previous study, participants were lived at the NIH and randomly received either a low-fat or a low-carbohydrate diet for 2 weeks and then switched to the other diet for 2 more weeks. Participants who received the low-carbohydrate diet first lost more body fat at the end of the study than those who received the low-fat diet first. Researchers want to see if they can repeat that result in a longer weight loss study when participants live at home. Objective: To test the effects of diet order in people receiving either a low-fat or low-carbohydrate diet first for 4 weeks and then immediately switched to the other diet for another 4 weeks. Eligibility: Adults aged 19 to 50 years with a body mass index of 25 or more. Design: Participants will complete the study at their homes, but there will be 3 required visits to the NIH. Participants will drink a special type of water 2 weeks before the baseline NIH visit and collect urine samples at home to measure how many calories they burn. Before the diets begin, participants will visit the NIH for baseline testing when they will have a metabolism test while relaxing in a bed with a plastic hood over their head to collect the air they breathe out. They will have scans to measure their bone density and how much muscle and body fat they have. They will give stool, blood, and urine samples. Participants will be asked to eat a specific diet for 4 weeks followed by a different diet for 4 weeks. All meals will be delivered to the participants homes. They will eat only the foods delivered. Participants will weigh themselves daily. They will wear a monitor to track their physical activity and a sensor to measure their glucose levels. They will prick their finger each morning to test a drop of blood for ketones. Participants will meet virtually as a group with the study team weekly. Participants will have two more NIH visits towards the end of each diet period....

Will I have to stop taking my current medications?

The trial requires that participants do not take prescription medications or other drugs that may influence metabolism, so you may need to stop taking certain medications if they affect your metabolism.

What data supports the effectiveness of low-carb and low-fat diets as treatments for obesity?

Research shows that low-carbohydrate diets can lead to more weight loss than low-fat diets in the short term (up to 6 months), with benefits like improved cholesterol levels. However, after 12 months, the weight loss differences between low-carb and low-fat diets are not significant. ^{1 2 3 4 5}

Are low-carb and low-fat diets safe for humans?

Both low-carb and low-fat diets have been shown to help with weight loss and reduce obesity-related health issues. However, the long-term safety of these diets has not been fully studied, so more research is needed to understand their effects over time. ^{3 6 7 8 9}

How does a low-fat diet differ from other treatments for obesity?

A low-fat diet, which is high in carbohydrates and plant-based, focuses on reducing fat intake to manage obesity, unlike low-carbohydrate diets that emphasize reducing carbs and increasing protein. While both can lead to weight loss, low-carbohydrate diets often result in more significant short-term weight loss, but the long-term benefits of low-fat diets may include better heart health due to lower saturated fat intake. ^{3 4 6 10 11}

Research Team

Valerie L Darcey

Principal Investigator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Eligibility Criteria

This trial is for adults aged 19 to 50 with a BMI of 25 or higher. Participants will follow and switch between low-fat and low-carb diets over an 8-week period, all while living at home. They must be willing to visit the NIH three times, track their weight daily, monitor physical activity and glucose levels, and attend virtual meetings.

Inclusion Criteria

Stated willingness to comply with all study procedures and availability for the duration of the study

Weight stable (< +/- 5 % over past 6 months) as determined by volunteer report

Body mass index (BMI) >= 25 kg/m2

Exclusion Criteria

Positive pregnancy test or lactating as determined by volunteer report (women only)

Inadequate access to equipment required for the study (e.g., too little refrigerator storage space or a microwave oven that is too small) as determined by discretion of PI and/or study team

Regular vigorous exercise >150 min per week as determined by volunteer report

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Baseline Testing

Participants undergo baseline testing including metabolism tests, scans for bone density, and collection of stool, blood, and urine samples

1 day

1 visit (in-person)

Diet Phase 1

Participants follow a specific diet (either low-fat or low-carbohydrate) for 4 weeks with meals delivered to their homes

4 weeks

1 visit (in-person), weekly virtual meetings

Diet Phase 2

Participants switch to the alternate diet (low-carbohydrate or low-fat) for another 4 weeks with meals delivered to their homes

4 weeks

1 visit (in-person), weekly virtual meetings

Follow-up

Participants are monitored for changes in body weight and fat mass, with final measurements taken

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• Low-carbohydrate Diet
• Low-fat Diet

Trial Overview The study tests whether starting with a low-carbohydrate diet leads to greater body fat loss compared to starting with a low-fat diet when each is followed for four weeks at home. Meals are provided, and participants' metabolism, bone density, muscle mass, body fat, and various health markers are monitored.

Participant Groups

Group I: low-fat diet then low-carbohydrate diet Experimental Treatment 2 Interventions

A low-fat followed by low-carbohydrate diet, each lasting for 4 weeks in adults with overweight or obesity

Group II: low-carbohydrate diet then low-fat diet Experimental Treatment 2 Interventions

A low-carbohydrate followed by low-fat diet, each lasting for 4 weeks in adults with overweight or obesity

Who Is Running the Clinical Trial?

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lead Sponsor

Trials

2,513

Recruited

4,366,000+

Findings from Research

Low-fat, high-complex carbohydrate diets can effectively promote weight loss in obese individuals, with a reduction of 10% in dietary fat leading to an average weight loss of about 5 kg, especially in those who adhere to the diet.

After significant weight loss, following an ad libitum low-fat diet is more effective for maintaining weight loss over two years compared to traditional caloric counting methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of low-fat diets and fat substitutes in body weight management: what have we learned from clinical studies? Astrup, A., Toubro, S., Raben, A., et al.[2019]

Meta-analyses of low-fat diets show significant weight loss (3-4 kg) in normal-weight and overweight individuals, indicating that reducing dietary fat is effective for weight management.

Replacing carbohydrates with protein in a low-fat diet can lead to greater weight loss, suggesting that protein is more satiating and beneficial for weight control compared to high-monounsaturated fat diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-fat diets and energy balance: how does the evidence stand in 2002? Astrup, A., Astrup, A., Buemann, B., et al.[2006]

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]

Low-carbohydrate diets can lead to greater initial weight loss (3-6 kg) compared to conventional low-fat diets, particularly noticeable at 6 months, but this difference diminishes after 12 months.

While low-carb diets do not increase LDL cholesterol and can improve HDL cholesterol and lower triglycerides, they may pose long-term health risks due to low intake of essential nutrients and fiber, making them unsuitable for general recommendation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Low-carbohydrate diets for obesity]. Keller, U., Rastalsky, N.[2008]

Low-fat diets in obese patients result in modest weight loss of 3-4 kg over 3 years, while calorie-controlled diets show better outcomes with 6-7 kg weight loss at 4 years, although long-term data is limited.

Bariatric surgery, such as gastric bypass, can lead to significant weight loss (up to 25% over 10 years) and reduce mortality and comorbidities, but it carries risks of nutritional deficiencies and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary treatment for obesity. Clifton, PM.[2022]

Low-carbohydrate diets lead to greater short-term weight loss compared to low-fat diets for overweight or obese individuals, particularly within the first 6 months.

There is currently a lack of research on the long-term safety and efficacy of both low-fat and low-carbohydrate diets for sustained weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial experience with fat-restricted vs. carbohydrate-restricted weight-loss diets. Klein, S.[2007]

In a 12-week study involving 55 obese participants, a high fat, low carbohydrate (HFLC) diet led to greater improvements in blood lipids and inflammation markers compared to a low fat, high carbohydrate (LFHC) diet, despite similar changes in body weight and composition.

The HFLC group experienced significant increases in HDL cholesterol and total adiponectin, along with decreases in serum triglycerides and hs-CRP, suggesting potential cardiovascular benefits from this dietary approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consuming a hypocaloric high fat low carbohydrate diet for 12 weeks lowers C-reactive protein, and raises serum adiponectin and high density lipoprotein-cholesterol in obese subjects. Ruth, MR., Port, AM., Shah, M., et al.[2022]

In a study of 82,802 women over 20 years, low-carbohydrate diets were not linked to an increased risk of coronary heart disease, suggesting they can be safe for long-term use.

Diets that emphasize vegetable sources of fat and protein, while being lower in carbohydrates, may even reduce the risk of coronary heart disease, highlighting the importance of food sources in dietary choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-carbohydrate-diet score and the risk of coronary heart disease in women. Halton, TL., Willett, WC., Liu, S., et al.[2022]

Low-carbohydrate diets (LCDs) significantly reduced HbA1c levels by 0.35% and led to greater body weight loss compared to low-fat diets (LFDs) in type 2 diabetes patients, based on a review of 12 randomized controlled trials involving 761 participants.

LCDs also improved cardiovascular risk factors by lowering triglycerides and increasing HDL cholesterol, with these benefits lasting up to 2 years, although the weight loss effects diminished after 2 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the Efficacy and Safety of Low-Carbohydrate Diets with Low-Fat Diets for Type 2 Diabetes Mellitus Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Li, S., Ding, L., Xiao, X.[2022]

In a study of 200 obese adults over six months, the low-carbohydrate ketogenic diet (LCKD) resulted in a significant weight loss of 13.0 kg compared to 4.7 kg with the low-caloric fat low diet (LCLF), indicating that LCKD is more effective for weight reduction.

The LCKD also led to greater reductions in fat mass and visceral fat, while not increasing cholesterol or uric acid levels, suggesting it is a safe and effective option for obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of low-carbohydrate ketogenic diet in the management of obesity compared with low caloric, low-fat diet. Al Aamri, KS., Alrawahi, AH., Al Busaidi, N., et al.[2022]

There is no evidence that increased fat intake is responsible for the rise in obesity, and diets with 30-35% of energy from fat can actually promote weight loss.

High-carbohydrate diets, especially those with a high glycaemic index, can lead to insulin resistance, but this can be countered by increased physical activity, highlighting the importance of exercise in managing diet-related health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High- versus low-fat diets in human diseases. Sanders, TA.[2019]

References

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

The role of low-fat diets and fat substitutes in body weight management: what have we learned from clinical studies? [2019]

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

Low-fat diets and energy balance: how does the evidence stand in 2002? [2006]

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. Switzerland pubmed.ncbi.nlm.nih.gov

[Low-carbohydrate diets for obesity]. [2008]

5. England pubmed.ncbi.nlm.nih.gov

Dietary treatment for obesity. [2022]

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

Clinical trial experience with fat-restricted vs. carbohydrate-restricted weight-loss diets. [2007]

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

Consuming a hypocaloric high fat low carbohydrate diet for 12 weeks lowers C-reactive protein, and raises serum adiponectin and high density lipoprotein-cholesterol in obese subjects. [2022]

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

Low-carbohydrate-diet score and the risk of coronary heart disease in women. [2022]

9. Egypt pubmed.ncbi.nlm.nih.gov

Comparing the Efficacy and Safety of Low-Carbohydrate Diets with Low-Fat Diets for Type 2 Diabetes Mellitus Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. [2022]

10. England pubmed.ncbi.nlm.nih.gov

The effect of low-carbohydrate ketogenic diet in the management of obesity compared with low caloric, low-fat diet. [2022]

11. England pubmed.ncbi.nlm.nih.gov

High- versus low-fat diets in human diseases. [2019]