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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different diets affect the body's internal clock, known as the circadian rhythm. Participants will alternate between a high-fat diet (also called a Low-Carb High-Fat Diet, Ketogenic Diet, or Atkins Diet) and a low-fat diet to observe how quickly their bodies adjust. The study spans 46 days, including time at home and in a clinic. Healthy, lean individuals without major dietary restrictions and who haven't worked irregular hours recently may be suitable candidates. As an unphased trial, this study allows participants to contribute to groundbreaking research on diet and circadian rhythms.

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.

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

Research has shown that high-fat diets, like the one under study, are generally easy for people to handle. Although some animal studies have raised concerns about how these diets might affect the body's internal clock, they remain safe for humans when balanced correctly.

Low-fat diets, also under investigation, are usually considered safe and are often recommended for good health. These diets contain less fat and more carbohydrates, which many people find easier to maintain over time.

Both types of diets have been extensively studied, and no major safety issues have been found in people who follow them carefully. Participation in this study will help researchers learn more about how these diets affect the body's internal clock. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the high-fat and low-fat diets being studied for their impact on circadian rhythm because these dietary approaches explore how macronutrient composition might regulate our body's internal clock. Unlike traditional treatments targeting sleep disorders through medication, these diets potentially offer a non-pharmacological approach that could align eating patterns with natural biological rhythms. The high-fat diet, with its unique balance of mono, poly, and saturated fats, may influence circadian rhythms differently compared to the low-fat option, which prioritizes carbohydrates. This trial could uncover new insights into how dietary fats and carbs affect our sleep-wake cycles, potentially leading to innovative lifestyle-based interventions for enhancing overall well-being.

What evidence suggests that this trial's diets could be effective for circadian rhythm?

This trial will compare the effects of a High-Fat Diet with a Low-Fat Diet on circadian rhythms. Research has shown that consuming fatty foods can disrupt the body's natural daily rhythms, known as circadian rhythms. This disruption links to changes in genes that regulate these rhythms and influence how the body processes food. Animal studies suggest that high-fat diets can alter the timing of these natural cycles, impacting metabolism and health. However, eating within a specific time frame, even with a high-fat diet, might mitigate some negative effects. Overall, high-fat diets interact with the body's internal clock, and meal timing may help reduce potential harm. ^{3 6 7 8 9}

Who Is on the Research Team?

Andrew McHill, PhD

Principal Investigator

Oregon Health and Science University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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 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]

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]

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]

Citations

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Chronobiology and Metabolism: Is Ketogenic Diet Able to ... High-fat diet and fasting influence circadian expression of clock genes, inducing phase-advance and phase-delay in animal models.

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Circadian rhythms, gut microbiota, and diet The TRF introduction in high-fat diet experiments has been shown to reverse many detrimental metabolic consequences and to positively affect gut microbial ...

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Circadian Rhythms, Diet and Neuronal Excitability - PMC Rodents fed a high-fat diet had altered expression of genes for enzymes involved in generating circadian time and metabolizing food. Molecular circadian clocks ...

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Effect of early vs. late time-restricted high-fat feeding on ... Although a high-fat (HF) diet leads to disrupted circadian rhythms, TRF can prevent metabolic diseases, emphasizing the importance of the timing ...

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Impact of Ketogenic Nutrition on Obesity and Metabolic Health Diets higher in healthy fats can modulate these hormones in a way that promotes satiety and reduces caloric intake, potentially making fat an ...

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The Influence of Ketone Bodies on Circadian Processes ... Among KDs, high-fat ketogenic diets (HFKD) contain a limited number of carbohydrates < 50 g/day, with ad libitum fat and calorie intake. While HFKD began as a ...

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Fasting, circadian rhythms, and time restricted feeding in ... High-fat diet disrupts behavioral and molecular circadian rhythms in mice. Cell metabolism. 2007;6:414–421. doi: 10.1016/j.cmet.2007.09.006. [DOI] [PubMed] ...

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Circadian misalignment in obesity: The role for time- ... Notably, TRF has been shown to protect against the obesogenic effects of a high-fat diet (HFD) [24]. ... Later circadian timing of food intake is associated with ...