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Metabolic and Bio-behavioral Effects of Following Recommendations in the Dietary Guidelines for Americans

Not Applicable
Recruiting
Conditions
Obesity
Body Weight
Interventions
Other: DGA Mediterranean diet pattern, negative energy balance
Other: DGA Mediterranean diet pattern, energy balance
Other: TAD diet pattern, negative energy balance
Registration Number
NCT04293224
Lead Sponsor
USDA, Western Human Nutrition Research Center
Brief Summary

This study, at the Western Human Nutrition Research Center (WHNRC), will focus on whether or not achieving and maintaining a healthy body weight is the most important health promoting recommendation of the Dietary Guidelines for Americans (DGA).The investigators hypothesize that improvement in cardiometabolic risk factors resulting from eating a DGA style diet will be greater in people whose energy intake is restricted to result in weight loss compared to those who maintain their weight. The investigators further propose that during a state of energy restriction, a higher nutrient quality diet such as the DGA style diet pattern, will result in greater improvement in cardiometabolic risk factors compared to a typical American diet (TAD) pattern that tends to be lower nutrient quality (more energy-dense and less nutrient-rich.)

Detailed Description

This will be a 28-week study including pre-diet testing (week 1), an 8-week controlled feeding period, post-diet testing (week 10), a follow-up period of dietary education and observation, and end of study testing (week 28). During the 8 week feeding, participants will be randomly assigned one of the following diets:

1. DGA Mediterranean diet pattern at sufficient energy level to maintain body weight (energy balance)

2. DGA Mediterranean diet pattern at a moderately reduced energy level (negative energy balance)

3. TAD diet pattern at a moderately reduced energy level (negative energy balance)

In the follow-up phase, the investigators will evaluate how multiple factors may influence body weight management, including previous dietary exposure, as well as the role of cognitive function, executive function, genetics, habitual diet, physical activity, eating behavior, stress and stress responsivity, metabolic flexibility and gut microbiome.

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
123
Inclusion Criteria
  • Body Mass Index (BMI) 23-39.9 kg/m2 or 32-50% body fat percentage
  • Willingness to have blood drawn
  • The criteria listed above and at least one of the following: Fasting glucose ≥100 mg/dL but <126 mg/dL or Fasting triglyceride ≥125 mg/dL or HDL-cholesterol ≤50 mg/dL or Blood Pressure (BP): Systolic BP ≥130 mmHg or Diastolic BP ≥85 mmHg or Hemoglobin A1C ≥ 5.7 and <6.5%
Exclusion Criteria
  • Active participation in another research study
  • Tested positive for COVID-19 within the past 10 days
  • Been in close contact with a COVID-19 positive person within the past 14 days
  • Blood Pressure (BP): Systolic BP ≥140 mmHg or Diastolic BP ≥90 mmHg
  • LDL cholesterol ≥190 mg/dL
  • Triglycerides ≥500 mg/dL
  • Current use of smoking or chewing tobacco, e-cigarettes, cigars, vaping, cannabis or other use of nicotine containing products (within the past 6 months)
  • Current use of dietary supplements and/or unwillingness to cease intake of dietary supplements
  • Vegan or vegetarian lifestyle or any other dietary restrictions that would interfere with consuming the intervention foods and beverages (including dietary intolerances, allergies and sensitivities)
  • Unwillingness to consume intervention foods and beverages
  • Engage in more than moderate drinking (> 1 drink serving per day) or binge drinking (4 drinks within two hours).
  • Unwillingness to cease alcohol intake as required for specific duration of the study
  • Excessive intake of caffeine containing products (excessive defined as ≥ 400 mg/day)
  • Unwillingness to refrain from caffeine intake on lab visit days.
  • Intentional weight change of ≥5% of body weight within 6 months of entry into the study
  • Diagnosis of disordered eating or eating disorder
  • Recent diagnosis of any of the following or measurement on screening lab tests: Anemia (hemoglobin <11.7 g/dL) or abnormal liver or thyroid function (defined as liver enzymes that are >200% of upper limit (ALT upper limit is 43 U/L or Aspartate transaminase (AST) upper limit is 54 U/L) and thyroid function tests: Thyroxine (T4, free) <0.56 or >1.64 ng/dL; Thyroid-stimulating hormone (TSH) <0.35 or >5.6 μIU/mL).
  • History of any of the following: Gastric bypass surgery, inflammatory bowel disease (IBD) or other GI conditions that would interfere with consuming the intervention foods, active cancer in the past three years excluding squamous or basal cell carcinomas of the skin that have been handled medically by local excision and other serious medical conditions
  • Recent dental work or have conditions of the oral cavity that would interfere with consuming the intervention foods and beverages
  • Taking any medication in the class of antipsychotics
  • Long term use of antibiotics
  • Taking any over the counter or prescribed medication for any of the following: Elevated lipids, elevated glucose, high blood pressure, weight loss or conditions that require corticosteroids (e.g. asthma, arthritis or eczema).
  • Are pregnant, planning to become pregnant within the duration of the study or breastfeeding.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DGA Mediterranean diet pattern, negative energy balanceDGA Mediterranean diet pattern, negative energy balanceNegative energy balance (\~25% calorie reduction compared to needs), emphasizes fruits, vegetables and whole grains and limits calories from added sugars and saturated fats and reduces sodium intake per Dietary Guidelines for Americans (DGA) recommendations.
DGA Mediterranean diet pattern, energy balanceDGA Mediterranean diet pattern, energy balanceDiet plan focused on energy balance (meets calorie needs), emphasizes fruits, vegetables and whole grains and limits calories from added sugars and saturated fats and reduces sodium intake per Dietary Guidelines for Americans (DGA) recommendations.
TAD diet patternTAD diet pattern, negative energy balanceTypical American Diet (TAD) with negative energy balance (\~25% calorie reduction compared to needs) which mimics intake of fruits, vegetables, whole grains, added sugars, saturated fats and sodium based on data from What We Eat in America (WWEIA).
Primary Outcome Measures
NameTimeMethod
Change in body weightMeasured weekly for weeks 1 through 10, and weeks 13, 17, 21, 24 and 28

Body weight will be measured to the nearest 0.1 kg using a calibrated electronic scale.

Secondary Outcome Measures
NameTimeMethod
Change in extracellular acidification rate (ECAR)Week 1 and 10

Measured in peripheral blood mononuclear cells by use of Seahorse XF Analyzer, a tool for measuring glycolysis and oxidative phosphorylation (through oxygen consumption) simultaneously in the same cells.

Change in waist circumferenceWeek 1, 10, 28

Waist circumference is measured with an anthropometric tape. Measurements will be performed in duplicate and averages recorded to the nearest 0.1 cm.

Change in hip circumferenceWeek 1, 10, 28

Hip circumference is measured with an anthropometric tape. Measurements will be performed in duplicate and averages recorded to the nearest 0.1 cm.

Change in body mass indexMeasured weekly for weeks 1 through 10, and weeks 13, 17, 21, 24 and 28

Body weight and height will be used to calculate Body Mass Index (BMI) as kg/m2.

Change in body fat (via DEXA scan)Week 1, 10, 28

Fat mass (grams) will be measured using dual energy x-ray absorptiometry (DEXA).

Change in resting systolic blood pressureWeek 1, 10, 28

Blood pressure will obtained via automated instrument and blood pressure cuff. At least two measurements will be made, expressed in mmHg, and the average value will be recorded.

Change in liver fatWeek 1 and 10

Liver fat assessed from the Controlled Attenuation Parameter (CAP) computed from the liver stiffness measurement using the Fibroscan®

Change in body water (via InBody)Week 1, 10, 28

Measured using bioelectrical impedance analysis (BIA) with an InBody 770® expressed as kg.

Change in waist to hip ratioWeek 1, 10, 28

Waist and hip circumference will be expressed as a ratio.

Change in resting diastolic blood pressureWeek 1, 10, 28

Blood pressure will obtained via automated instrument and blood pressure cuff. At least two measurements will be made, expressed in mmHg, and the average value will be recorded.

Change in liver stiffnessWeek 1 and 10

Liver stiffness assessed from the shear wave speed with pulse echo ultrasound using the Fibroscan®

HeightWeek 1

Height will be measured to the nearest 0.1 cm using a wall-mounted stadiometer.

Change in resting heart rateWeek 1, 10, 28

Resting heart rate (pulse) will obtained via automated instrument in beats per minute.

Genetic Risk of ObesityWeek 1

Genomic DNA will be collected from white blood cells. A polygenic risk score (PRS) indexing genetic predisposition to obesity using known obesity single nucleotide polymorphisms (SNPs).

Change in hemoglobin A1CWeek 1, 10, 28

This outcome will evaluate glycated hemoglobin as a reflection of the plasma glucose level during the past two to three months.

Change in urinary potassiumWeek 1, 5, 7 and 10

Urinary potassium will be measured as indicators of dietary compliance during the feeding intervention of the study. All urine passed for a 24 hour period will be collected.

Change in C-reactive proteinWeek 1, 10, 28

C-Reactive Protein will be measured as a non-specific marker for inflammation.

Change in total cholesterolWeek 1 and 10

Total cholesterol will be collected to evaluate cardiac risk expressed as milligrams per deciliter (mg/dL).

Change in vascular healthWeek 1, 5, 10

Peripheral Arterial Tone (PAT) technology will be used to measure vascular health. The EndoPAT test is a non-invasive measurement of the overall health of the endothelium.

Change in red blood cell fatty acidsWeek 1, 10, 28

Red blood cell fatty acids will be analyzed by mass spectrometry (MS).

Change in high density lipoprotein (HDL) cholesterolWeek 1 and 10

HDL cholesterol will be collected to evaluate cardiac risk expressed as milligrams per deciliter (mg/dL).

Change in triglycerides in response to a mealBaseline and 1, 2, 3, and 6 hours after a challenge meal

Triglycerides will be measured in blood (mg/dL).

Change in blood metabolite profilesWeek 1 and 10

Analysis of metabolites, the small molecule substrates, intermediates and products of metabolism analyzed by mass spectrometry (MS). Includes branched chain amino acids, 2 hydroxybutyric acid, acylcarnitines, saturated, monounsaturated and polyunsaturated non-esterified fatty acids, triglyceride species, phospholipid species, bile acids and steroid hormones.

Change in fasting blood glucoseWeek 1, 10, 28

This outcome will evaluate blood sugars levels in the fasted state.

Change in urinary sodiumWeek 1, 5, 7 and 10

Urinary sodium will be measured as indicators of dietary compliance during the feeding intervention of the study. All urine passed for a 24 hour period will be collected.

Change in urinary nitrogenWeek 1, 5, 7 and 10

Urinary nitrogen will be measured as indicators of dietary compliance during the feeding intervention of the study. All urine passed for a 24 hour period will be collected.

Change in carotenoid levelsWeek 1 and 10

Serum carotenoids, including vitamin A, alpha-carotene, and beta-carotene will be used to evaluate nutrient status and dietary intake of vegetables prior to feeding intervention and post feeding intervention.

Change in low density lipoprotein (LDL) cholesterolWeek 1 and 10

LDL cholesterol will be collected to evaluate cardiac risk expressed as milligrams per deciliter (mg/dL).

Change in allostatic loadWeek 1, 10, 28

Allostatic load (AL) is an aggregate value derived from several parameters that assess physiologic adaptive response to neural or neuroendocrine stressors. The following measures are used to determine the AL score: Urinary cortisol and catecholamine levels, resting blood pressure, waist to hip ratio, blood levels of high sensitivity C-Reactive Protein, cholesterol, dehydroepiandrosterone sulfate and hemoglobin A1c, and urinary levels of epinephrine and norepinephrine.

Change in perceived stressWeek 1, 6, 10, 19 and 28

Perceived stress measured using the Perceived stress scale (PSS). Scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress. Responses for individual questions are summed to a total score.

Barriers to physical activityWeek 1

Participants will be asked to complete the Barriers to Being Active questionnaire.

Usual physical activityWeek 1

An accelerometer (Actical) will be continuously worn by participants during waking hours (excluding bathing and swimming) for a period of 7 days.The measure of usual physical activity is used to estimate total energy expenditure and energy requirements.

Diet acceptabilityWeek 10

This measurement is an evaluation of palatability, ease of preparation, satisfaction, and perceived benefits and adverse effects related to a prescribed controlled feeding diet.

Change in heart rate variabilityWeek 1 and 10

Autonomic physiological functioning will be assessed using the MindWare Cardio/Galvanic Skin Response (GSR) system, a device that connects to the subject's torso with eight disposable electrodes and a heart rate monitor. Emotional arousal via skin conductance, a form of electrodermal activity (EDA) is also measured.

Change in ghrelin in response to a mealBaseline and 1, 2, 3, and 6 hours after a challenge meal

Ghrelin will be evaluated as an indicator of hunger signaling.

Change in leptin in response to a mealBaseline and 1, 2, 3, and 6 hours after a challenge meal

Leptin will be evaluated as an indicator of satiety signaling.

Change in Matsuda IndexBaseline and 1, 2 hours after a challenge meal

Matsuda index will be calculated from plasma glucose and insulin.

Change in executive functionWeek 1 and 10

Assessed using Cambridge Gambling Task (CGT), from Cambridge Neuropsychological Test Automated Battery (CANTAB).

Change in verbal memoryWeek 1 and 10

Assessed using Verbal Recognition Memory (VRM) task from Cambridge Neuropsychological Test Automated Battery (CANTAB).

Change in spatial memoryWeek 1 and 10

Assessed using Spatial Working Memory (SWM) task from Cambridge Neuropsychological Test Automated Battery (CANTAB).

Change in multitaskingWeek 1 and 10

Assessed using Multitasking Test (MTT) from Cambridge Neuropsychological Test Automated Battery (CANTAB).

Change in social cognitionWeek 1 and 10

Assessed using Emotional Recognition (ERT) task from Cambridge Neuropsychological Test Automated Battery (CANTAB).

Change in attentive functionWeek 1 and 10

Assessed using Stop Signal Task (STT) from Cambridge Neuropsychological Test Automated Battery (CANTAB).

Change in insulin in response to a mealBaseline and 1, 2, 3, and 6 hours after a challenge meal

Insulin measured in blood using an antibody based assay. Will also be expressed as the quantitative insulin sensitivity check index (QUICKI).

Change in resting metabolic rateWeek 1 and 10

Respiratory gas exchange measurements (oxygen consumption-VO2 and carbon dioxide production-VCO2) will be made to determine metabolic rate using a metabolic cart system.

Change in post-prandial metabolic rate1, 2, 3 and 6 hours after a meal

Post-prandial metabolic rate measured using indirect calorimetry.

Change in metabolic flexibilityWeek 1 and 10

The formula is designed to deliver approximately 800 kcals total with 60% kcals from fat (approximately 55 g of fat), 25% kcals from carbohydrates, and 15% of kcals from protein.

Change in predicted VO2 maxWeek 1, 10, 28

Cardiorespiratory endurance will be evaluated by measuring heart rate (HR) and oxygen consumption (VO2) during a walking graded exercise test on a treadmill.

Change in interstitial glucose levelsWeek 1 and 10

A continuous glucose monitor (CGM) will be used to continuously assess interstitial glucose levels. The Abbott Freestyle Libre Pro Sensor is inserted under the skin on the back of the arm. The sensor will measure the interstitial glucose level every fifteen minutes. Participants will wear the monitors for fourteen days.

Change in response speedWeek 1 and 10

Assessed using Motor Screening Task (MOT), from Cambridge Neuropsychological Test Automated Battery (CANTAB).

Change in fecal microbiomeWeek 1, 10 an 28

Assays will be performed on fecal samples to determine DNA representing the colonic microbiota.

Change in psycho-motor speedWeek 1 and 10

Assessed using Reaction Time (RTI) task from Cambridge Neuropsychological Test Automated Battery (CANTAB).

Change in continuous systolic blood pressureWeek 1 and 10

Blood pressure measured using a Continuous Non-invasive Arterial Pressure (CNAP®) device in mmHg.

Change in continuous diastolic blood pressureWeek 1 and 10

Blood pressure measured using a Continuous Non-invasive Arterial Pressure (CNAP®) device in mmHg.

Change in moodWeek 1 and 10

Mood assessed using the Profile of Mood States (POMS). Total Mood Disturbance (TMD) score is found from the difference between "negative" subscales - "positive" subscales. Individual scores on the POMS range from -32 to 200 with higher scores indicating higher mood disturbance.

Change in diet satisfactionWeek 1, 19 and 28

This 28 item questionnaire acts as a valid instrument for assessing diet satisfaction in the context of weight-management. This measurement assesses diet satisfaction both within and outside the context of weight-loss treatment, as well as to assesses change in satisfaction as a result of treatment.

Change in Food ChoiceWeek 1 and 10

Food choice computer-based tests from Leeds, United Kingdom, will be used to estimate explicit liking and implicit wanting for several different categories of foods.

Change in oxygen consumption rate (OCR)Week 1 and 10

Measured in peripheral blood mononuclear cells by use of Seahorse XF Analyzer, a tool for measuring glycolysis and oxidative phosphorylation (through oxygen consumption) simultaneously in the same cells.

Change in mean arterial blood pressureWeek 1 and 10

Blood pressure measured using a Continuous Non-invasive Arterial Pressure (CNAP®) device in mmHg .

Change in self-efficacyWeek 10, 19 and 28

This 20 item questionnaire is a measurement of the capacity to execute behaviors necessary to change their weight and begin to implement exercise in their lives regularly.

Change in appetiteWeek 1 and 10

A computer tablet with stylus will be used to assess hunger and appetite, defined as perceived hunger, fullness, desire to eat, prospective consumption and other measures of food craving and perceived hypoglycemia. Questions will be presented one-by-one on the screen and participants will be asked to express their response using visual analog scales (VAS). This measurement will be evaluated during the meal challenge assessment.

Three factor eating questionnaireWeek 1 and 10

This 18 item questionnaire is used to examine three dimensions of human eating behavior including cognitive restraint, disinhibition or uncontrolled eating and hunger.

Yale Food Addiction ScaleWeek 1

Measures markers of substance dependence with the consumption of high fat/high sugar foods. This is a 25-item self-report measure that includes mixed response categories (dichotomous and Likert-type format).

Changes in dietary intakeWeek 1, 19, and 28

Three non-consecutive twenty-four hour dietary recalls will be collected when subjects are self-selecting their 'usual' diets. A three day average nutrient intake will be expressed.

Change in stress reactivityWeek 1 and 10

Acute stress reactivity will be assessed by measuring salivary cortisol concentrations in response to a challenging task.

Trial Locations

Locations (1)

UC Davis, Western Human Nutrition Research Center

🇺🇸

Davis, California, United States

UC Davis, Western Human Nutrition Research Center
🇺🇸Davis, California, United States
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