Low Sugar Protein Pacing, Intermittent Fasting Diet in Men and Women

Study Overview
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Brief Summary
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This study will systematically quantify the effects of protein pacing and intermittent fasting (P-IF) on total and regional (abdominal) body composition (lean mass and fat mass), blood glucose and lipids, and anti-aging biomarkers, hunger ratings, and the gut microbiome in 40 overweight/obese adult men (n=20) and women (n=20) following a 8-week weight loss intervention. Participants will be enrolled in the study as a single cohort and participate in a 8-week weight loss (WL) trial consisting of a single dietary intervention phase. The purpose of the additional 12 month follow up case study (in addition to the initial 12-month case study period) is to scientifically document a significant weight loss and improved body composition following combined protein pacing intermittent fasting nutrition and a safe, effective exercise program in a study participant who achieved successful weight loss maintenance during the previous 12 month follow up study period.

Detailed Description
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Previous research has shown combined protein pacing and intermittent fasting (PP-IF; 1-2 days per week) combined with moderate (20-30%) caloric restriction (CR) favorably enhance weight loss, body composition, cardiometabolic disease risk, oxidative stress, and toxin levels compared to a heart healthy diet in obese individuals following both weight loss and weight loss maintenance (Arciero et al. 2016; He et al. 2017; Zuo et al. 2016). However, less is known about whether a low sugar intake with this dietary pattern induces other significant health improvements, such as enhanced brain health (mood state), as well as gut microbiome and anti-aging indices, compared to a heart healthy diet. The novelty of the current proposal is of particular relevance and importance given the heightened popularity of low sugar dietary patterns shown to enhance health status. Most notably, among these low sugar diets touting the health benefits, are the ketogenic, paleolithic and Mediterranean diets. In addition, there is a great deal of public health emphasis on reducing overall carbohydrate intake, especially simple sugars, to improve cardiometabolic, gut, and body composition health. The dangers of high simple sugar intake are numerous, including increased risk for cardiometabolic disease (high blood lipids, hyperglycemia, insulin resistance, systemic inflammation, oxidative stress, obesity, elevated visceral fat, etc.). Thus, improvements in body composition and reductions in disease risk provides compelling evidence to pursue this study with vigor so as to generate a viable and healthy weight and fat loss strategy over the long term. Another major factor to augment long-term (>1 year) weight loss success, is inclusion of a safe and realistic exercise program (4 days/week) consisting of walking, stretching, and simple body weight movements such as sit-ups and push-ups. To date, there are no documented case studies of a human participant achieving a one hundred pound plus weight loss using protein pacing and intermittent fasting combined with a proven, safe and time-efficient exercise program. The purpose of this study is to compare the effects of a low sugar protein pacing, intermittent fasting (P-IF) diet versus a heart healthy (HH) diet on indices of body weight, total and regional body composition, mood state, anti-aging, and cardiometabolic outcomes, and the gut microbiome during weight loss (0-8 weeks). Specifically, this study aims to compare a P-IF diet comprised of a calorie-restricted (1500 calories/day women; 1800 calories/day men) protein pacing diet (P, 4 meals/day women, 5 meals/day men) followed by a fast (IF,  350-450 kcals/day) compared to an established calorie-restricted (1200 calories/day for women; 1500 calories/day men) heart healthy (HH) diet. The P-IF group will be divided into two subgroups for weeks 1-4. One subgroup will consist of five days of P and two days of IF, and the second subgroup will consist of six days of P and one day of IF. For weeks 5-8 both subgroups will follow 6 days of a P diet and 1 day IF. The purpose of the additional 12 month follow up case study (in addition to the initial 12-month case study period) is to scientifically document a significant weight loss and improved body composition following combined protein pacing intermittent fasting nutrition and a safe, effective exercise program in a study participant who achieved successful weight loss maintenance during the previous 12 month follow up study period.

Official Title
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Comparison of Protein Pacing, Intermittent Fast vs. Heart Healthy Diet on Body Weight and Composition, Cardiometabolic, Mood, and Gut Microbiome Health, in Overweight Men and Women During Weight Loss; 24 Months Follow-up Case Study of 100 Pound Weight Loss in a Male Study Participant

Conditions
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Weight Loss, Gut Microbiome, Anti-Aging

Intervention / Treatment
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* Behavioral: P-IF
* Behavioral: HH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-smoking, healthy, but overweight/obese men and women with no known cardiovascular or metabolic diseases as assessed by a medical history and a comprehensive medical examination by their physicians Sedentary or lightly active (<30 min, 2d/wk of structured physical activity) as assessed by a Physical Activity questionnaire Overweight or obese (BMI>27.5 kg/m2; % body fat>30%) Weight stable (+/-2kg) for at least 6 months prior to beginning the study Exclusion Criteria: Type II Diabetes Emphysema Significant heart disease (CABG, CHF, VFib, Hypercholesterolemia, Uncontrolled High Blood Pressure, etc.) COPD Cancer or undergoing treatment for cancer Allergies to milk or milk products, sugar alcohols, fructose, or gluten Anorexia or Bulimia Fasting intolerances/hypoglycemia Pregnant or plan to become pregnant during 8-week study

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 40 overweight/obese adult men (n=20) and women (n=20) will be quasi-randomized to one of the two groups matched by sex (men/women) and body weight. Participants will be enrolled in the study as a single cohort and participate in a 8-week weight loss (WL) trial consisting of a single dietary intervention phase. A single male participant from the original P-IF group will continue following the identical P-IF from the original 4-8 week phase and 12 month follow up period (5-6 days of P; 1-2 day of IF) for an additional 12 month period (beyond the initial 12 monthfollow up case study period). The participant will consume the identical P-IF meal plan as the original 8 week study and 24 month follow up.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Protein pacing and intermittent fasting<br>During the 8-week weight loss (WL) phase, participants assigned to the P-IF will consist of P days, whereby female participants will consume four and male participants will consume five meals/snacks total, two of which (breakfast and lunch) will include a protein powder meal replacement mixed with water (240-400 kcals per meal) along with an evening dinner meal ( 500 kcals), an afternoon snack (men only), and an evening snack (250 kcals). Subjects will be calorie restricted to  1500 and  1800 calories per day, women and men, respectively during P days. For each IF day, subjects will be provided a variety of supplements/snacks made by Isagenix International LLC. The P-IF group will be further divided into two subgroups for weeks 1-4. One subgroup will consist of five days of P and two days of IF, and the second subgroup will consist of six days of P and one day of IF. For weeks 5-8 both subgroups will follow 6 days of a P diet and 1 day IF. | Behavioral: P-IF<br>* Protein pacing and intermittent fasting<br>|
| Experimental: Heart Healthy<br>The HH group will observe the dietary guidelines in compliance with the National Cholesterol Education Program Therapeutic Lifestyle Changes (TLC) diet. This diet consists of consuming <35% of kcal as fat; 50%-60% of kcal as carbohydrates; <200 mg/dL of dietary cholesterol; and 20-30 g/day of fiber. The total calorie intake will be 1200 and 1500 calories per day, women and men, respectively during the weight loss phase (weeks 0-8). | Behavioral: HH<br>* Heart Healthy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight | Total body weight measurement | 0 weeks, 4 weeks, 8 weeks and monthly intervals during the 2 year Case Study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in total and regional body fat and lean body mass | Quantitative measure of total body fat and lean mass using iDXA (dual x-ray absorptiometry) | 0 weeks, 8 weeks, 1 year and 2 year of the Case study | 
| Changes in feelings of hunger, fullness, satiety scores measured with a visual analog scale | Hunger ratings using a visual analog scale ranging from 0-100 mm. A score closer to 0mm indicates no level of hunger related feelings and a score of 100 mm indicates extreme hunger-related feelings | 0 weeks, 4 weeks, 8 weeks and monthly intervals during the 2 year Case Study | 
| Change in blood lipid levels | Venipuncture blood draw of 5ml per visit (weeks 0 and 8) and a single finger stick* of 40ul (week 4); *Finger stick at week 4 will only measure glucose and blood lipids | 0 weeks, 4 weeks, 8 weeks and every 6 months during the 2 year Case Study | 
| Change in gut microbiome, gastrointestinal symptoms, stool | Fecal gut microbiome communities will be sequenced using microbial DNA extracted from samples at 0, 4, and 8 weeks for each study arm. Amplified copies of the 16S rRNA gene will be evaluated for treatment differences in alpha (within-sample richness and evenness) and beta diversity (between-sample community structure). Relative and differential abundance of individual microbial taxa will also be measured. In addition, GI symptoms will be assessed using the Gastrointestinal symptom questionnaire and stool quality will be assessed with the Bristol stool chart | 0 weeks, 4 weeks, 8 weeks and two month intervals during the 2 year Case Study | 
| Change in blood pressure | Quantitative measure of blood pressure using automated blood pressure monitor called a mobiligraph for 1 minute | 0 weeks, 4 weeks, 8 weeks and monthly intervals during the 2 year Case Study | 
| Change in heart rate | Quantitative measure of heart rate using automated heart rate monitor called a mobiligraph for 1 minute | 0 weeks, 4 weeks, 8 weeks and monthly intervals during the 2 year Case Study | 
| Change in fat mass and muscle mass | Quantitative measure of total body fat and muscle mass using BODPod (air displacement plethysmography) | 0 weeks, 4 weeks, 8 weeks and monthly intervals during the 2 year Case Study | 
| Change in physical activity | Quantitative measure of physical activity (kilocalories per day) using the ActiGraph accelerometer | 0 weeks, 4 weeks, 8 weeks, and monthly intervals during the 2 year of the Case study | 
| Change in energy intake | Quantitative measure of energy intake (kilocalories per day) using the 2-day food diary | 0 weeks, 4 weeks, 8 weeks, and monthly intervals during the 2 year of the Case study |