Controlled Feeding Diets for Healthy Eating

Overseen By Frank M Sacks, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Harvard School of Public Health (HSPH)

Must not be taking: Diuretics, Steroids, NSAIDS, Opiates

Disqualifiers: Gastrointestinal conditions, Cancer, Heart disease, others

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

Compensation: Varies

Number of Visits: 26

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study how different foods affect the body by controlling participants' diets. Researchers will explore how eight foods influence the body over a single day and compare the effects of ten foods over time. The trial suits healthy adults who can attend all study visits and adhere to the Controlled Feeding Diet. Participants should not have gastrointestinal issues or major food allergies. As an unphased trial, this study allows participants to contribute to valuable nutritional research that could inform future dietary guidelines.

Do I need to stop taking my current medications for the trial?

You may need to stop taking certain medications. Over-the-counter weight-loss aids, anti-inflammatories, and some dietary supplements must be stopped during feeding periods. Prescription medications like diuretics, steroids, NSAIDs, opiates, and others listed in the exclusion criteria may disqualify you from participating. However, some medications like nasal or topical steroids, aspirin, and certain psychiatric drugs are allowed. It's best to discuss your specific medications with the trial staff.

What prior data suggests that these controlled feeding diets are safe?

Research has shown that diets used in similar studies have been well-tolerated by participants. Safety data from past research indicate that foods tested in controlled environments generally do not cause harmful effects. For example, studies on how different foods affect the body have demonstrated their safety, even in various amounts.

In studies examining how the body processes food, participants tolerated the foods well, whether consumed on an empty stomach or with a meal. This indicates that eating these foods did not lead to significant health problems for the participants.

Although the exact foods and amounts used in this trial are not specified, similar studies have generally confirmed their safety in healthy people. This suggests a low risk of negative side effects for participants during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these controlled feeding diets because they offer a structured approach to understanding how different levels of food intake impact health. Unlike typical dietary recommendations that often rely on self-reported data, these diets provide precise control over what participants eat, allowing for more accurate insights. The Dose Response diet examines the effects of varying food quantities over six days, which could reveal optimal intake levels for health benefits. The Pharmacokinetic diet focuses on how specific foods impact the body in a single day, providing a snapshot of immediate metabolic responses. Together, these approaches aim to refine dietary guidelines and improve eating habits based on robust scientific evidence.

What evidence suggests that this trial's dietary interventions could be effective for healthy eating?

Research has shown that controlled feeding diets can improve health. In this trial, participants will join one of two different controlled feeding diet arms. The Pharmacokinetic arm involves a single-day intervention with 10 test foods, while the Dose Response arm spans six days with three levels of controlled feeding (zero, medium, high dose). Studies have found that these diets aid in weight management and promote healthier eating habits. Specifically, planned dietary changes have successfully helped people lose weight, suggesting a positive impact on health. Additionally, research has discovered that nutrient intake can influence health outcomes. While the specific foods and their effects are still under study, evidence supports the potential health benefits of controlled feeding diets. ^{1 2 3 6 7}

Who Is on the Research Team?

Frank M Sacks, MD

Principal Investigator

Harvard School of Public Health (HSPH)

Jonathan S Williams, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for healthy adults over 18 with a BMI of 18.5-39.9 kg/m2 who are willing to attend all study visits. It's not suitable for those with certain gastrointestinal conditions, recent severe heart issues, active cancer treatments, significant weight changes recently, high blood pressure, or specific dietary restrictions and medication use.

Inclusion Criteria

Your body weight is within a healthy range, neither too low nor too high.

Willingness to participate in all study visits

Exclusion Criteria

You have a very high body weight compared to your height.

I have a bleeding disorder that makes blood draws unsafe.

Hypertension- seated blood pressure >140 mmHg or diastolic >90 mmHg

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pharmacokinetic (PK)

Participants complete a sequence of dietary intakes of up to 8 test foods in a randomized, crossover study. Blood and urine samples are collected for metabolomic analysis.

8 days

8 visits (in-person)

Dose Response (DR)

Participants undergo an isocaloric, controlled feeding study examining three dose levels for 10 foods in five pairings over six days each.

18 days

18 visits (in-person)

Follow-up

Participants are monitored for biomarker changes post consumption of test foods.

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Dose Response (DR)- Controlled Feeding Diet
• Pharmacokinetic (PK)- Controlled Feeding Diet

Trial Overview The trial is testing how the body processes eight different foods in a crossover design (each participant tries each food) and compares the effects of ten foods in both parallel-group and crossover designs to understand dose-response relationships.

How Is the Trial Designed?

Group I: Pharmacokinetic Experimental Treatment 1 Intervention

Single Day Intervention of 10 test foods

Group II: Dose Response Experimental Treatment 1 Intervention

Six day, 3 level (zero, medium, high dose) controlled feeding study

Who Is Running the Clinical Trial?

Harvard School of Public Health (HSPH)

Lead Sponsor

Trials

283

Recruited

17,030,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In an 8-week controlled-feeding trial involving two diet patterns (Dietary Guidelines for Americans and a typical American diet), both diets were found to be acceptable to participants, with over 95% adherence to the provided foods.

The study highlighted challenges in meeting specific nutrient intake recommendations, particularly for vitamins D and E, dietary fiber, and the sodium-to-potassium ratio, indicating the complexity of designing effective dietary interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges in Designing and Delivering Diets and Assessing Adherence: A Randomized Controlled Trial Evaluating the 2010 Dietary Guidelines for Americans. Krishnan, S., Lee, F., Burnett, DJ., et al.[2022]

The American Dietetic Association emphasizes that medical nutrition therapy is essential for managing chronic conditions and should be integrated with pharmacotherapy for optimal treatment outcomes.

A coordinated team approach involving dietetics professionals and other healthcare members is crucial for the success of both medical nutrition therapy and pharmacotherapy, ensuring effective management and monitoring of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Position of the American Dietetic Association: medical nutrition therapy and pharmacotherapy. [2006]

Rats on a 34% fat diet showed an increased threshold dose for the appetite-suppressing hormone cholecystokinin-8 (CCK-8), indicating that higher fat intake may reduce the hormone's effectiveness in inhibiting food intake, although this was only replicated in one of the three experiments.

In contrast, rats on a 60% fat diet demonstrated increased potency of CCK-8, with a lower threshold dose and a significantly more potent dose-response function, suggesting that very high fat diets can enhance the appetite-suppressing effects of CCK-8.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two effects of high-fat diets on the satiating potency of cholecystokinin-8. Torregrossa, AM., Smith, GP.[2019]

Highly processed foods, particularly those high in fat and glycemic load, are significantly associated with addictive-like eating behaviors, as shown in studies involving 504 participants across two different settings.

The study suggests that not all foods contribute equally to addictive-like eating, with processed foods sharing pharmacokinetic properties similar to drugs of abuse, indicating a potential link between food composition and problematic eating patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which foods may be addictive? The roles of processing, fat content, and glycemic load. Schulte, EM., Avena, NM., Gearhardt, AN.[2022]

Human eating behavior is influenced by a combination of physiological, sensory, psychological, and environmental factors, which are crucial for understanding and addressing diseases like obesity and diabetes.

The increase in portion sizes in North America over recent decades is identified as a significant environmental factor contributing to the rise in obesity prevalence, highlighting the need for clinicians and nutritionists to consider these behavioral insights when modifying diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Why should we study human food intake behaviour? Bellisle, F.[2019]

In a controlled feeding study with 153 postmenopausal women, serum biomarkers for vitamins and carotenoids were found to effectively reflect dietary intake, showing strong correlations with nutrient consumption.

The study suggests that these serum biomarkers can serve as reliable indicators of nutrient intake, similar to established urinary recovery biomarkers for energy and protein, although further research is needed to assess fatty acid intake measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary biomarker evaluation in a controlled feeding study in women from the Women's Health Initiative cohort. Lampe, JW., Huang, Y., Neuhouser, ML., et al.[2023]

A multicomponent approach to treating pediatric overweight/obesity, which includes behavioral strategies, is recommended, but specific dietary interventions lack strong guidelines.

The review found that more structured dietary interventions (like controlling food types and amounts) lead to better weight outcomes, with longer interventions (≥6 months) showing greater reductions in body mass index compared to shorter ones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of structure in dietary approaches for the treatment of pediatric overweight and obesity: A critical review. Griffiths, LA., Douglas, SM., Raynor, HA.[2021]

Intestinal fat, particularly long-chain free fatty acids, plays a significant role in regulating appetite by stimulating the release of the satiety hormone cholecystokinin (CCK), which helps signal fullness to the brain.

CCK not only aids in digestion by promoting gallbladder contraction and pancreatic secretion but also inhibits gastric emptying and appetite, acting as both a positive feedback signal for digestion and a negative feedback signal to limit food intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fat in the intestine as a regulator of appetite--role of CCK. Beglinger, C., Degen, L.[2006]

Appetite disturbances play a significant role in obesity, influenced by a complex interaction of internal factors (like genetics and brain chemistry) and external factors (such as environment and diet).

Effective treatment of obesity requires controlling appetite through various methods, including regulating food supply, cognitive strategies, environmental changes, or pharmacological interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Appetite disturbance and the problems of overweight. Blundell, JE.[2018]

The safety assessment of food ingredients in the 21st century will combine traditional methods, like the 'safe' dose concept, with modern techniques such as Benchmark Dose (BMD) and physiologically-based pharmacokinetic models to improve accuracy.

Emerging research in toxicology may further enhance risk assessment methods, suggesting that a multi-faceted approach will be essential for evaluating food ingredient safety effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in assessing ingredient safety. Dourson, ML., York, RG.[2017]

In a pilot study involving children aged 8-12 with severe obesity, structured dietary interventions led to significant reductions in BMI, with a median change of -1.2 kg/m2 for individualized menu plans and -1.8 kg/m2 for those receiving both menus and meals.

Both dietary approaches were well-received by families, indicating that structured dietary interventions could be a promising strategy for managing severe pediatric obesity and should be explored further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structured Dietary Interventions in the Treatment of Severe Pediatric Obesity: A Pilot Study. Kalarchian, MA., Levine, MD., Marcus, MD.[2021]

In a study involving 83 healthy subjects, food intake significantly increased the maximum plasma concentration (C max) of hydrocodone ER by 40% after a single dose, indicating that food can affect the immediate absorption of the medication.

However, after multiple doses of hydrocodone ER, the pharmacokinetics showed no clinically meaningful food effects at steady state, suggesting that the impact of food on drug absorption diminishes with regular use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Food on the Pharmacokinetics of Single- and Multiple-Dose Hydrocodone Extended Release in Healthy Subjects. Bond, M., Rabinovich-Guilatt, L., Selim, S., et al.[2018]

The FDA's Total Diet Study (TDS) has been ongoing since the 1960s to monitor pesticide residues and contaminants in food, with the latest update in 2003 reflecting changes in food consumption patterns, including a shift towards lower-fat foods.

The updated TDS food list, which includes 285 foods, shows an increase in total food consumption, particularly in grains and beverages, highlighting the importance of adapting dietary exposure estimates to current eating habits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update of US FDA's Total Diet Study food list and diets. Egan, SK., Bolger, PM., Carrington, CD.[2022]

Recent updates to dietary risk assessment methodologies now better account for consumer exposure to residue levels, improving the accuracy of chronic exposure assessments.

A new short-term exposure assessment method has been developed that considers portion sizes and variability in residue levels, but further data on portion sizes and unit weights is needed for international implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Joint FAO/WHO Geneva consultation--acute dietary intake methodology. Crossley, SJ.[2007]

The safety of substance intake is determined by its toxic potential, the amount consumed, and individual biological factors, highlighting the complexity of assessing health risks.

Establishing safe intake levels requires adequate data on adverse effects, which varies by nutrient; some nutrients have enough data to determine safe limits, while others do not.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety limits for nutrients. Hathcock, JN.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4811006/

Intervention Engagement Moderates the Dose–Response ... Significant changes over time and time × group effects revealed the effectiveness of the intervention. The effect of the intervention (time 1) on changes in ...

2. withpower.com withpower.com/trial/phase-healthy-diet-2023-99256

Controlled Feeding Diets for Healthy Eating The available research shows that structured dietary interventions, which include controlled feeding diets, are effective in improving weight outcomes, ...

3. ajcn.nutrition.org ajcn.nutrition.org/article/S0002-9165(22)02934-3/fulltext

A randomized controlled-feeding trial based on the Dietary ... The DGA and TAD diets had respective Healthy Eating Index scores of 98 and 62. All foods and beverages were provided during the intervention.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12026834/

Mapping the Quantitative Dose–Response Relationships ... This review identified significant dose–response relationships across 12 nutrients and their associations with various health outcomes.

5. sciencedirect.com sciencedirect.com/org/science/article/pii/S2561672222000463

Dose-Response Relationship of a Blended In-Person and ... The aims of this paper are to examine families' engagement patterns with the EIP and to evaluate the dose-response relationship between EIP engagement patterns ...

6. cdn.who.int cdn.who.int/media/docs/default-source/food-safety/publications/chapter5-dose-response.pdf

Chapter 5 Dose–response assessment and derivation of ... As EHC 240 focuses on risk assessment of chemicals in food, the derivation of HBGVs for oral (dietary) exposures is discussed in this chapter. A key step in.

7. efsa.europa.eu efsa.europa.eu/en/supporting/pub/en-1899

Dose‐response relationships in health risk assessment of ... A flexible and powerful tool to comprehensively summarize and model the relation between dietary constituents and health endpoints based on epidemiologic ...