Nutritional and Metabolic Diseases

All Conditions

Symptoms and General Pathology

Metabolic Diseases

Weight Loss

Obesity

Body Weight

Obesity, Abdominal

Overweight

Overnutrition

Nutrition Disorders

Body Weight Changes

2 days per week fasting with 25 % energy intake and 5 days per week at 100% energy intake

diet intervention to reduce the risk for obesity associated diseases

Calorie Restriction

Tilman Kühn, PhD

This study evaluates the effect of intermittent calorie restriction versus continued calorie restriction on weight loss, gene expression profile of subcutaneous adipose tissue and abdominal fat distribution.

Since obesity has become a major public health concern appropriate strategies are needed in order to reduce obesity-related health risks in later life span. Obesity is one of the main risk factors not only for diabetes and cardiovascular diseases, but also for several types of cancer. Several key mechanisms, which may link obesity, metabolic dysregulation and cancer risk, such as obesity-driven inflammation, altered adipokine, growth factor and sex hormone signaling, and changes in the microbiota have been identified.

Various studies have shown that continuous calorie restriction (CCR) and exercise are effective strategies to enforce weight-loss and improve biomarker profiles. Intermittent calorie restriction (ICR) as a novel strategy might induce favorable metabolic changes and lead to higher compliance rates. The concept of this diet regime is very simple e.g. 2 days/week of fasting following a standardized diet covering 25 % of energy needs and 5 days/week of ad libitum consumption. To verify the effectiveness of ICR as an alternative weight loss strategy to CCR controlled intervention trials are required. Although both CCR and ICR induce a negative energy balance, the metabolic effect on human physiology might differ.

Within the HELENA-study 50 non-smoking adults (men and women aged 35 to 65 years) with an BMI ≥ 25 kg/m² and ≤ 40 kg/m² will be randomly assigned to each of the intervention arms: (1) ICR arm (2 day/week fasting, i.e. 25% energy intake, energy intake of 100% on 5 days/week leading to a weekly average energy intake of \~80%) (2) CCR arm (daily energy intake of 80%) and 3) control arm (general advice on healthy nutrition).

The trial will last 1 year, with an intervention phase of 12 weeks (weeks 0-12; intervention; close contact with participants), followed by a maintenance phase (weeks 13-24; maintenance; regular, but less frequent contact with participants) and a follow-up phase (weeks 25-52).

Biological specimens will be collected as follows:

Baseline (T0, week 1): Blood, urine, stool and subcutaneous adipose tissue samples; After 3 months (T1, week 13): Blood, urine, stool and subcutaneous adipose tissue samples; After 6 months (T2, week 25): Blood, urine, and stool; After 12 months (T3, week 52): Blood and urine; Magnet resonance tomography imaging (MRI, at T0, T1 and T3) and lifestyle assessments (nutrition behavior, physical activity and quality of life, T0-T3) will be performed to unravel the link to fat distribution, metabolic changes, health and lifestyle. The primary objective of the three-arm randomized controlled intervention trial is to investigate the effect of nutrition intervention on body weight and gene expression profile in subcutaneous adipose tissue of overweight and obese individuals. We hypothesize that better compliance rates will be achieved by the ICR rather than by the CCR group and that ICR will show a higher sustainability with respect to weight loss, weight maintenance, and biomarker profiles. The purpose of this study is further to analyze if the nutrition interventions and associated weight loss have different effects on abdominal fat distribution and liver fat content.

The statistical analysis will be carried out by using the SAS statistical software \[SAS Institute Inc., Cary, NC, USA\] or comparable software. Descriptive statistics, correlations and univariate analyses will be used to get insight on general characteristics of participants in the intervention groups. For the primary objective, two sided t-test and ANCOVA modelling will be performed to investigate whether changes in gene expression levels are affected by nutrition intervention. Comparisons between two groups (e.g. ICR and CCR or CCR/ICR and control group) will be carried out using t-tests and parallel comparison across the three groups will be carried out using ANCOVA models. Where applicable, the analyses will include adjustments for confounders, specially age and gender. Likewise, stratified analysis will be carried out as necessary. ANCOVA models will be performed to evaluate the effects of nutrition intervention on biomarker profiles, adjusted by strata age and gender. Similar evaluations will be performed for fat distribution patterns, quality of life, physical activity and nutrition patterns. In addition, correlation and linear regression analyses will be performed to measure effects of weight-loss, gene expression levels and metabolic profiles, controlled by nutrition intervention group.

Nutrition and Energy Restriction for Cancer Prevention

Healthy Nutrition and Energy Restriction as Cancer Prevention Strategies: a Randomized Controlled Intervention Trial

University Hospital Heidelberg

German Cancer Research Center

Dr. Tilman Kühn

Neoplasms

Skin and Connective Tissue Diseases

Inflammation

Recurrence

Breast Neoplasms

Breast Diseases

Skin Diseases

Anti-Inflammatory Agents

All Drugs and Chemicals

The Diabetes Prevention Program-based lifestyle change intervention (DPP) is designed to help overweight breast cancer survivors to reduce their risk of breast cancer recurrence by reducing their excess body fat.

The Highly Microbiota-Accessible Foods (HMAFs) lifestyle change intervention is designed to help overweight breast cancer survivors reduce their risk of breast cancer recurrence by reducing their elevated low-grade inflammation.

The DPP condition consists of 11 health education sessions over 12 weeks, including 2 virtual home visits, two virtual group education sessions and 7 telephone coaching calls. These sessions will teach DPP-based lessons on how to lose excess body fat through calorie restriction and increased physical activity. All dietary and physical activity recommendations are intended to be consistent with federal nutrition and physical activity guidelines.

Diabetes Prevention Program-based lifestyle change intervention (DPP)

The Highly Microbiota-Accessible Foods (HMAFs) intervention approach includes 11 health education sessions, including two virtual home visits, two virtual group education sessions, and 7 telephone coaching sessions. These sessions are designed to help study participants to identify and consume optimally 6 daily instances of minimally processed, fiber-rich food sources, drawn from all four of the MyPlate.gov categories: vegetables, fruits, whole grains and plant-based protein-rich foods (e.g., legumes, nuts and seeds). Increased physical activity is also recommended as a way to optimize the microbial conversion of fiber-rich food sources to short chain fatty acids, which are then expected to reduce excess low-grade inflammation.

Highly Microbiota-Accessible Foods (HMAFs) intervention

William J. McCarthy, Ph.D.

Wendy Rue, B.A.

Jacqueline Wong, B.A.

William J McCarthy, Ph.D.

William J. McCarthy

Pilot randomized controlled parallel group behavior change comparative effectiveness trial involves 30 breast cancer survivors interested in losing excess body fat. Both interventions include dietary + exercise prescriptions that hold promise for reducing the survivors' risk of cancer recurrence. Both interventions are consistent with the Dietary Guidelines for Americans but the Diabetes Prevention Program (DPP)-based approach focuses on weight loss through calorie restriction and increased physical activity while the Highly Microbiota-Accessible Foods (HMAFs) approach is intended to be a low-numeracy version of a Mediterranean-style diet and increased physical activity. The DPP approach is considered to be a high-numeracy intervention because it requires that consumers keep track of all calories consumed and expended per day and to endeavor to maintain a calorie deficit each day during the active weight loss phase. For both conditions, the 12 to 13-week intervention includes 2 virtual home visits, 2 virtual group education sessions and 7 telephone or Zoom-based coaching sessions by well-trained intervenors. Assessments occur at baseline and six months, with systemic inflammation (high sensitivity C-reactive protein) being the primary outcome measure and visceral fat being a secondary outcome. Other prespecified secondary outcomes include gut microbiota alpha-1 diversity, insulin resistance, HDL-cholesterol, daily count of highly microbiota-accessible foods, waist circumference, BMI, systolic blood pressure, ratio of fecal Proteobacteria to short chain fatty acid-generating bacteria and health-related quality of life.

Background. The human gut microbiota influences obesity status and inflammation, two major risk factors for postmenopausal breast cancer recurrence. Whether an exercise and dietary intervention designed to optimize gut microbiota composition might reduce risk for breast cancer recurrence is unknown. To improve the gut microbiota composition, the investigators propose teaching postmenopausal breast cancer survivors to allocate about 20% of their daily calorie intake to consuming a daily count of six fiber-rich, minimally processed, plant-based food choices that comply with federal MyPlate.gov diet recommendations. Preliminary data suggest that the investigators' Highly-Microbiota-Accessible Foods (HMAFs) approach will yield cardiometabolic outcomes equal to or better than those achieved by the traditional Diabetes Prevention Program (DPP) calorie restriction approach at 6 months follow-up. Because breast cancer recurrence risk covaries with cardiometabolic risks, the lower cardiometabolic risk of the HMAFs approach should be associated with reduced risk of breast cancer recurrence.

Hypotheses. The greater diversity of fiber-rich, minimally processed plant foods consumed in the HMAFs condition relative to the DPP condition will result in greater changes in HMAFs participants compared to DPP participants from baseline to 6 months follow-up in the following measures: (primary hypothesis) reduce high sensitivity C-reactive protein, (secondary hypotheses) reduce visceral body fat and increase alpha-1 diversity of gut microbes and increase health-related quality of life.

To test these hypotheses, the research objectives include the following specific aims: 1) Recruit a diverse sample of 30 overweight or obese postmenopausal survivors with stage I, II and IIIa breast cancer; randomly allocate them to two lifestyle change intervention conditions, 2) Obtain baseline and 6-month follow-up assessments of: low grade systemic inflammation, body composition including visceral fat estimation, cardiorespiratory fitness, inflammatory and cardiometabolic biomarkers, fecal samples, and quality of life, 3) Conduct two parallel, three-month behavior change interventions, contrasting the 6-count HMAFs approach with the traditional DPP calorie restriction approach , and 4) Use results to design a ramped-up randomized factorial trial.

If hypotheses are confirmed, the low-numeracy HMAFs approach may, for low-income survivors, be a practical alternative to traditional high-numeracy calorie restriction approaches to reducing risk of breast cancer recurrence.

The two lifestyle change interventions feature a similar exercise prescription and the same sequence of intervention contacts (2 virtual home visits; 2 virtual group education sessions, 7 individual telephone coaching sessions) but differ in dietary approach. The DPP-based diet approach prescribes desired weight loss in overweight breast cancer survivors by restricting daily calorie intake and promoting increased calorie expenditure via physical activity. The HMAFs approach prescribes consuming an optimal six microbiota-accessible foods unaccompanied by pro-inflammatory food components such as saturated fat or added sugar as well as engaging regularly in exercise that elevates the heart rate and reduces inflammation. Only 20 percent of daily calories need to be devoted to HMAFs; the remaining calories can come from daily food choices conforming to the 2020-2025 Dietary Guidelines for Americans.

All assessments will be conducted by project personnel blind to the study participants' randomization status. The investigators responsible for helping participants complete the Automated Self-administered 24-hour (ASA 24) dietary recalls and for assessing their body composition via dual x-ray absorptiometry (DXA) will be kept blind to the study participants' randomization status. Investigators will be kept blind to participant assignment to condition by having the two health coaches refer to their patients by an arbitrary, unique study identifier during weekly debriefings when the study progress by individual participants might be discussed.

UCLA Breast Cancer Survivor Health Promotion Research Study

A Fiber-diverse, Anti-inflammatory Diet and Aerobic Exercise Reduce Risk of Breast Cancer Recurrence

De-identified data will be posted on the website of the UCLA Fielding School of Public Health for access by students and other investigators. Primary and secondary outcomes and demographic characteristics will be shared.

Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) is a recognized measure of insulin resistance, calculated from fasting glucose and fasting insulin values

Waist circumference is measured via non-stretchable measuring tape around the waist at a midpoint between the lowest rib and the iliac crest, upon breath exhalation.

Height measured via wall-mounted stadiometer and weight measured via calibrated digital scale will be used to compute BMI ((kg/(m x m))

Regularly calibrated digital sphygmomanometer will be used to assess the participant's resting systolic blood pressure in millimeters of mercury

Fecal DNA from the V4 region of the 16S ribosomal RNA will be amplified, sequenced and filtered for quality before statistical analysis. The ratio of fecal Proteobacterial abundance to the abundance of short-chain fatty acid-generating fecal microbes is expected to be reduced in healthier guts.

RAND Short Form-20 (SF-20) is recognized instrument for assessing participants' health-related quality of life. Minimum score = 0; maximum score = 100. Higher scores represent higher quality of life.

Fasting serum HDL-cholesterol concentration expected to reflect the experimental differences in dietary patterns. Serum triglycerides will be generated as part of a standard lipid panel.

CRP is commonly used by researchers as a biomarker for systemic inflammation.

Visceral fat is also known as intra-abdominal fat. It is located inside the peritoneal cavity, packed in between internal organs and torso. It is the most metabolically active adipose tissue and positively associated with systemic inflammation.

Fecal DNA from the V4 region of the 16S ribosomal RNA will be amplified, sequenced and filtered for quality before statistical analysis. The Shannon index measures both gene richness and evenness.

From participants' 24-hour diet recalls - The daily sum of different carbohydrate-rich food sources minimally processed and unaccompanied by pro-inflammatory components, especially saturated fat and added sugar.

University of California, Los Angeles

Adjunct Professor

Subjects will follow all study tasks but will not be required to follow a calorie-restricted meal plan.

Subjects in this arm will be asked to alternate between one day of eating as they wish versus one day on a calorie-restricted meal plan. Subjects will follow this alternating meal plan for 3 months.

Subjects in this arm will be asked to follow a calorie-restricted meal plan, daily, for three months.

Subjects in the "calorie restriction" arm and the "alternate day fasting" arm will be asked to follow a menu plan, for three months, that includes some level of calorie restriction.

calorie restriction

Marc Hellerstein, MD, PhD

The purpose of this study is to examine and compare the effects of alternate-day reductions in calorie intake or daily calorie restriction on the risk for cardiovascular disease and cancer.

Overweight individuals are at greater risk for certain chronic diseases such as cardiovascular disease and cancer when compared to those who are normal weight. Dietary restriction has been shown to lower the risk of these chronic diseases in overweight human subjects as well as in normal weight rodents. The majority of studies examining dietary restriction protocols in rodents or humans implement daily calorie restriction (CR), i.e. where the amount of energy consumed is decreased by a certain percentage every day. Another dietary restriction regimen employed, although less commonly, is intermittent caloric restriction, or alternate-day fasting (ADF), i.e. where food is available ad-librium every other day, alternating with a partial or complete caloric restriction day. Recent findings suggest that ADF may modulate certain indices of disease risk to a similar extent as daily CR in animal models. The effect of ADF regimens in comparison with CR regimens on disease risk has yet to be performed in human subjects, however. ADF protocols need not result in weight loss, and would therefore be appropriate for non-obese individuals. Accumulating evidence suggest that adipose tissue may play a role in modulating chronic disease risk by releasing substrates, such as fatty acids, or a variety of hormones, including adiponectin and leptin. The effect of ADF and CR on adipose tissue metabolism and hormone release remains unclear. Accordingly, the aim of the present study is to compare ADF regimes to CR for their effects on risk factors for cardiovascular disease and cancer and their effects on adipose tissue metabolism and hormone secretion, in normal weight to modestly overweight (BMI 22-27 kg/m2) human subjects.

Effect of Daily Calorie or Alternate-day Calorie Reductions on Risk for Cardiovascular Disease and Cancer

Effect of Daily Calorie Restriction or Alternate-day Reductions in Calorie Intake on Risk for Cardiovascular Disease and Cancer

Parameters measured will include adipose tissue dynamics (triglyceride turnover, lipolysis, de novo lipogenesis, adipose cell proliferation), adipose tissue morphology (cell size and number), adipose tissue hormone levels (adiponectin, leptin), skin turnover (keratin dynamics), T-lymphocyte proliferation, as well as plasma lipid and lipoprotein, homocysteine, and C-reactive protein levels.

National Institutes of Health (NIH)

University of California, San Francisco

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Central Nervous System Depressants

Herbal and Botanical

Other Dietary Supplements

Benzocaine

Tannic Acid

During the active weight loss period, the TRE group will be instructed to eat ad libitum from 12:00pm - 8:00pm daily and fast from 8:00pm - 12:00pm. During the 8-h eating window, there will be no restrictions on types or quantities of foods consumed. During the fasting period, participants will be encouraged to drink plenty of water and may consume energy-free beverages, such as black tea or coffee. TRE subjects will meet with the TRE dietitian for 30 minutes at the start of the intervention to review instructions and goals, and then every week throughout the active weight loss period to review intervention adherence. At the beginning of the maintenance phase, total energy needs will be reassessed. Subjects will be instructed to main their body weight by consuming meals in an extended 10-h eating window every day and water fast between 8pm and 10 am, respectively.

Cal-R subjects will be instructed to restrict energy intake by 25% of their baseline total energy expenditure (TEE) daily. Subjects will meet with a study dietitian for a 60-min one-on-one session to develop individualized weight loss meal plans to help them adhere to their calorie restriction goal. Meal plans will include portion sizes and food lists that are consistent with their food preferences and prescribed calorie levels for weight loss. Food scales will be provided to help with food portioning. Cal-R subjects will meet with the dietitian every week throughout the weight loss period to review intervention adherence and modify the meal plans as needed. Subjects will be asked to maintain their baseline level of physical activity. At the beginning of the weight maintenance phase, total energy needs will be reassessed.

Controls will be instructed to maintain their weight throughout the 12 m trial and to not change eating or physical activity habits. Controls will not receive dietary counseling. Controls will visit the research center every 3 months for outcome measurements.

daily ad libitum food intake, 8-h 12pm - 8pm, 6 m active weight loss phase; 10-h 10am-8pm, 6 m maintenance phase

Time restricted eating

daily 25% calorie restriction, 6 m active weight loss phase; 100% energy needs, 6 m maintenance phase

Lisa Tussing-Humphreys, PhD, MS, RD

Krista Varady, PhD

Lisa Tussing-Humphreys

Approximately 42% of American adults are obese, and this condition is strongly related to the development of colorectal cancer. Innovative lifestyle strategies to treat obesity and reduce colorectal cancer risk are critically needed. This research will demonstrate that time-restricted eating, a type of intermittent fasting, is an effective therapy to help obese individuals reduce and control their body weight and prevent the development of colorectal cancer.

Approximately 42% of the U.S. adult population is obese and data suggests that persons with obesity are at a 30% greater risk of developing colorectal cancer (CRC). Therefore, efficacious approaches to preventing and treating obesity will have significant effects on CRC incidence in the U.S. Although calorie restriction through lifestyle intervention is the most common approach to treat obesity, clinically meaningful weight loss is difficult to achieve via this method due to low adherence with calorie monitoring, indicating a need for innovation. Time-restricted eating, a type of intermittent fasting, has been shown in animals to impart cancer protective effects including lower body weight, decreased systemic inflammation, and improved glucose metabolism. Time-restricted eating is where individuals are asked to consume all their food for the day within a specified time frame, and water fast for the remaining hours of the day. We recently performed two short-term (≤12-weeks) pilot studies of time-restricted eating to evaluate its safety and preliminary efficacy on body weight and chronic disease risk markers in adults with obesity. Our results show the intervention is a safe and acceptable approach to weight loss among obese adults. Moreover, time-restricted eating produced approximately 3% weight loss from baseline and reductions in systolic blood pressure, oxidative stress and insulin resistance. Although these pilot findings show promise for time-restricted eating as an effective tool for CRC risk reduction among obese individuals, these data still require confirmation by a well powered longer-term clinical trial. The present proposal aims to implement a 12-month (6-month intervention, 6-month maintenance) controlled, parallel arm trial among 255 obese adults (45-70 years old) who have had a colonoscopy. Subjects will be randomized to 1 of 3 groups: 1) 8-hour time-restricted eating (daily ad libitum food intake from 12pm - 8pm), 2) Calorie restriction (daily 25% calorie restriction), or 3) Control (daily ad libitum food intake, no meal timing restrictions) to compare the effects on: (1) Body weight, body composition, and intervention adherence; (2) Circulating metabolic, inflammation, and oxidative stress-related biomarkers; (3) Colonic mucosal gene expression profiles and mucosal inflammation, DNA damage and cellular growth; and (4) maintenance of benefits on body weight/composition and CRC markers.

Subjects will be randomized by the data manager, by way of a stratified random sample in 1:1:1 ratio. The sample frame will be divided into strata based on BMI, sex, and age. Subjects from each stratum, will then be randomized to 1 of 3 groups: 1) TRE, 2) Cal-R, or 3) Control.

Time-restricted Eating Versus Daily Continuous Calorie Restriction on Body Weight and Colorectal Cancer Risk Markers

Effects of Time-restricted Eating Versus Daily Continuous Calorie Restriction on Body Weight and Colorectal Cancer Risk Markers Among Adults With Obesity

Total and regional body fat composition and distribution will be measured via whole body DEXA scan

Measured through electronic diet records and 24 hour dietary recalls

From fasting venous blood measured by a commercial lab

Commercially available targeted transcriptomics platform

Healthy colonic mucosa, immunohistochemistry

Healthy colonic mucosa, immunohistochemistry,

From fasting venous blood measured at a commercial lab

calculated from fasting glucose and insulin using a standard formula

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nutrition and Energy Restriction for Cancer Prevention	NCT02449148	Obesity Visceral Obesit... Weight Loss Metabolic Disea... Body Compositio...	Calorie Restric...	35 Years - 65 Years	German Cancer Research Center
UCLA Breast Cancer Survivor Health Promotion Research Study	NCT05113485	Breast Cancer	Diabetes Preven... Highly Microbio...	50 Years - 75 Years	University of California, Los Angeles
Effect of Daily Calorie or Alternate-day Calorie Reductions on Risk for Cardiovascular Disease and Cancer	NCT00467220	Moderately Over...	calorie restric...	35 Years - 65 Years	University of California, San Francisco
Time-restricted Eating Versus Daily Continuous Calorie Restriction on Body Weight and Colorectal Cancer Risk Markers	NCT05114798	Time Restricted... Obesity Weight Loss Colorectal Canc...	Time restricted... Calorie Restric...	45 Years - 70 Years	University of Illinois at Chicago

Spots Global Cancer Trial Database for calorie restriction