High-Fat vs Low-Fat Diet for Circadian Rhythm

(FACT Trial)

Overseen By Andrew McHill, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Oregon Health and Science University

Must not be taking: Prescribed medications, Over-the-counter

Disqualifiers: Drug/alcohol use, High-fat diet, others

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

Compensation: Varies

Number of Visits: 5

14 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking any prescribed or over-the-counter medications to participate in this trial.

What data supports the effectiveness of the high-fat vs low-fat diet treatment for circadian rhythm?

Research shows that low-carbohydrate, high-fat (LCHF) diets can lead to significant weight loss and improvements in conditions like type 2 diabetes and high blood pressure. These diets may also reduce hunger, which can help with weight management. ^{1 2 3 4 5}

Is a high-fat or low-fat diet generally safe for humans?

Research shows that low-carbohydrate, high-fat diets can be effective for weight loss and managing conditions like diabetes and high blood pressure, but there are concerns about long-term heart health risks. Low-fat diets are also effective for weight loss and may be preferred for heart health, but more long-term studies are needed to fully understand the safety of both diets. ^{1 2 6 7 8}

How does the High-Fat vs Low-Fat Diet treatment affect circadian rhythm?

The High-Fat vs Low-Fat Diet treatment is unique because it explores how different diet compositions, particularly high-fat and low-fat diets, can influence circadian rhythms (the body's internal clock) and metabolic processes. The ketogenic diet, a type of high-fat diet, can induce a metabolic switch that mimics fasting, potentially altering circadian gene expression and offering new approaches to managing obesity and metabolic disorders. ^{3 6 9 10 11}

What is the purpose of this trial?

The goals of this study are to uncover the influence of diet on the human circadian timing system. The protocol is a 46-day (28 outpatient days, 18 inpatient days over two 9 day visits) randomized cross-over study designed to elucidate the speed of entrainment in response to a high-fat diet.

Research Team

Andrew McHill, PhD

Principal Investigator

Oregon Health and Science University

Eligibility Criteria

This trial is for healthy, lean men and women who don't smoke or use drugs, have no major health issues like heart disease or diabetes, and haven't worked night shifts in the past year. They should not be on any medications or other research studies that could affect their safety.

Inclusion Criteria

I am healthy and maintain a normal weight.

Exclusion Criteria

I have a kidney or urinary tract disorder.

I have a disorder affecting my immune system.

Currently psychiatrically/psychologically unsuitable for participation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ambulatory Monitoring

Participants maintain a consistent 14-day at home 8h sleep schedule at habitual times before both laboratory visits

2 weeks

Daily monitoring (virtual)

Outpatient Diet

Participants consume an outpatient isocaloric diet designed to meet individual daily energy requirements

2 weeks

3 visits (in-person) or meal delivery

Inpatient Protocols

Participants undergo in-laboratory measurements of circadian timing, entrainment, and other physiological markers

18 days

2 visits (inpatient, 9 days each)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• High-Fat Diet
• Low-Fat Diet

Trial Overview The study tests how a high-fat diet versus a low-fat diet affects our body's internal clock over a period of 46 days with both outpatient and inpatient phases. Participants will switch diets at some point to compare effects.

Participant Groups

Group I: High-Fat Diet Experimental Treatment 1 Intervention

50% fat, 35% carbohydrate and 15% protein; 33% of each mono, poly and saturated fat

Group II: Low-Fat Diet Active Control 1 Intervention

30% fat, 55% carbohydrate and 15% protein

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

In a study of 100 volunteers adhering to a low carbohydrate high fat (LCHF) diet, participants maintained a very low carbohydrate intake (8.7 E%) and a high fat intake (72.0 E%), indicating that such a diet can be sustained over time without apparent nutrient deficiencies.

However, the diet raised concerns due to high levels of saturated fat (32 E%) and cholesterol (700 mg/day), which exceed recommended limits, alongside a very low intake of dietary fiber, suggesting potential long-term cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low carbohydrate high fat-diet in real life assessed by diet history interviews. Hagström, H., Hagfors, LN., Tellström, A., et al.[2023]

In a study of 127 individuals following a low-carbohydrate, high-fat (LCHF) diet, participants reported an impressive total weight loss of 1,900 kg, with an average loss of 15 kg, indicating significant potential for weight management with this eating plan.

The LCHF diet not only led to substantial weight loss but also resulted in improvements in various medical conditions, with many participants reporting reduced medication needs for type 2 diabetes, hypertension, and other health issues, suggesting a possible therapeutic benefit beyond weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-carbohydrate and high-fat intake can manage obesity and associated conditions: occasional survey. Noakes, TD.[2018]

Diets with a daily calorie deficit of 500-1000 kcal can lead to weight losses of 300 to 1000 grams per week, depending on the individual's starting weight, highlighting the importance of calorie control in weight loss programs.

Very low-energy diets (200-800 kcal per day) are used but lack strong evidence for effectiveness below 800 kcal, while higher-protein diets have shown better results compared to low-protein diets in promoting weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary approaches to reducing body weight. Astrup, A.[2019]

A low-carbohydrate, high-fat (LCHF) dietary intervention in a primary care setting led to significant reductions in weight (3.96 kg) and body mass index (BMI) (1.46 kg/m2) among 122 patients who attended at least 2 educational sessions.

Patients who attended more than 5 educational sessions showed greater improvements in various health markers, including blood pressure and HbA1c, indicating that higher compliance with the LCHF program is associated with better health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of a primary care low-carbohydrate, high-fat dietary educational intervention on laboratory and anthropometric data of patients with chronic disease: a retrospective cohort chart review. Myshak-Davis, AT., Evans, J., Howay, H., et al.[2022]

In a study of 944 children with severe burns, those on a low-fat/high-carbohydrate diet (Vivonex T.E.N.) experienced significantly shorter ICU stays and lower rates of sepsis compared to those on a high-fat diet (milk).

Patients on the low-fat diet also showed less organ enlargement and hepatic steatosis at autopsy, suggesting that a high carbohydrate/low fat nutrition approach may lead to better clinical outcomes in burn care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between dietary fat content and outcomes in pediatric burn patients. Lee, JO., Gauglitz, GG., Herndon, DN., et al.[2021]

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 study involving 227 adults, participants lost an average of 11.1 kg (9.8%) after following three different dietary interventions, indicating that sequential dieting can lead to significant weight loss.

Approximately 78.6% of participants achieved at least a 5% weight loss with one of the diets, suggesting that various dietary approaches, including low-carbohydrate high-fat (LCHF) and time-restricted feeding (TRF), can be effective for weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential diets and weight loss: Including a low-carbohydrate high-fat diet with and without time-restricted feeding. Christensen, RAG., High, S., Wharton, S., et al.[2021]

A review of eight studies involving 1217 overweight and obese adults found that both very low carbohydrate high fat (VLCHF) and low fat (LF) diets led to significant weight loss and improvements in blood pressure and blood glucose levels over a duration of up to 24 months.

While VLCHF diets increased HDL cholesterol and reduced triglycerides, they also had higher saturated fat content compared to LF diets, and adherence to VLCHF was often poor without intensive support from health professionals, indicating a need for careful monitoring of dietary fat intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring the highs and lows of very low carbohydrate high fat diets on weight loss and diabetes- and cardiovascular disease-related risk markers: A systematic review. Ross, LJ., Byrnes, A., Hay, RL., et al.[2021]

Circadian rhythms play a crucial role in regulating energy metabolism, and misalignment between the central clock in the brain and peripheral clocks in the body can lead to metabolic diseases, particularly affecting shift workers who make up 20% of the workforce.

Recent animal studies suggest that a ketogenic diet can modify circadian gene expression and induce metabolic changes, potentially offering new treatment strategies for obesity and metabolic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronobiology and Metabolism: Is Ketogenic Diet Able to Influence Circadian Rhythm? Gangitano, E., Gnessi, L., Lenzi, A., et al.[2021]

In a study of 172 middle-aged Italian adults, those with an evening chronotype were found to have a higher body mass index (BMI) and lower adherence to the Mediterranean diet (MD), indicating a link between chronotype and unhealthy lifestyle choices.

The research suggests that assessing chronotype could be important in managing obesity and developing effective nutritional strategies, as evening chronotypes were associated with poorer dietary habits and higher obesity rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronotype and Adherence to the Mediterranean Diet in Obesity: Results from the Opera Prevention Project. Muscogiuri, G., Barrea, L., Aprano, S., et al.[2022]

The Mediterranean diet, characterized by its balanced intake of macronutrients and micronutrients, is recommended for long-term weight maintenance and health benefits, unlike short-term restrictive diets that are difficult to sustain.

Low-carbohydrate ketogenic diets may pose medical risks, particularly for individuals with obesity, as they can lead to metabolic acidosis and renal issues, potentially reducing life expectancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-carbohydrate ketogenic diets in body weight control: A recurrent plaguing issue of fad diets? Schutz, Y., Montani, JP., Dulloo, AG.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Low carbohydrate high fat-diet in real life assessed by diet history interviews. [2023]

2. South Africa pubmed.ncbi.nlm.nih.gov

Low-carbohydrate and high-fat intake can manage obesity and associated conditions: occasional survey. [2018]

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

Dietary approaches to reducing body weight. [2019]

4. England pubmed.ncbi.nlm.nih.gov

The effects of a primary care low-carbohydrate, high-fat dietary educational intervention on laboratory and anthropometric data of patients with chronic disease: a retrospective cohort chart review. [2022]

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

Association between dietary fat content and outcomes in pediatric burn patients. [2021]

6. 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]

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

Sequential diets and weight loss: Including a low-carbohydrate high-fat diet with and without time-restricted feeding. [2021]

8. Australia pubmed.ncbi.nlm.nih.gov

Exploring the highs and lows of very low carbohydrate high fat diets on weight loss and diabetes- and cardiovascular disease-related risk markers: A systematic review. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Chronobiology and Metabolism: Is Ketogenic Diet Able to Influence Circadian Rhythm? [2021]

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

Chronotype and Adherence to the Mediterranean Diet in Obesity: Results from the Opera Prevention Project. [2022]

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

Low-carbohydrate ketogenic diets in body weight control: A recurrent plaguing issue of fad diets? [2021]