Diets for Reducing Abdominal Fat in Obesity

((HDLS2) Trial)

Overseen By Carol J Boushey, PhD, RDN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Hawaii

Must not be taking: Anti-estrogens, Anti-androgens, Insulin

Disqualifiers: Pregnancy, Diabetes, Thyroid conditions, others

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

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

260 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining intermittent fasting (IER) with a Mediterranean diet (MED) reduces belly fat more effectively than daily calorie restriction (DER) with the same diet. Both methods will also be evaluated for their effects on cancer risk markers and gut health. The trial targets individuals of East Asian, Native Hawaiian, Pacific Islander, or White ethnicity living on Oahu with high belly fat. Participants will adhere to a specific diet and exercise plan to determine which method proves more effective over 24 weeks. As an unphased trial, it offers participants the opportunity to contribute to groundbreaking research on diet and health.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking anti-estrogen or anti-androgen medications, or insulin for diabetes, you may not be eligible to participate.

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

Research shows that both the IER+MED and MED/DER diets are generally safe for participants. In past studies, the IER+MED diet reduced body fat and improved insulin resistance without major safety issues. Participants tolerated this diet well, with no serious problems reported.

The MED/DER diet has also demonstrated weight loss benefits. It significantly reduced body weight and body fat when combined with reduced calorie intake. These studies found no major safety concerns, and participants usually experienced only mild side effects.

Overall, both diets appear safe and well-tolerated based on current research. Participants in similar studies generally did not experience serious side effects, suggesting these diets could be a safe option for reducing belly fat. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because they explore how different dietary approaches can effectively target abdominal fat in obesity. The IER+MED method is unique because it incorporates intermittent energy restriction, meaning it significantly cuts calorie intake for just two days a week while maintaining a Mediterranean diet on other days. This approach could be easier for some people to stick to compared to traditional daily calorie restriction. On the other hand, the MED/DER method consistently reduces daily calorie intake while emphasizing a balanced diet rich in healthy fats, which might lead to more gradual and sustained weight loss. Both methods also encourage moderate exercise, aiming to enhance fat reduction results.

What evidence suggests that this trial's diets could be effective for reducing abdominal fat in obesity?

Research has shown that combining intermittent energy restriction with a Mediterranean diet (IER+MED), one of the treatment arms in this trial, effectively reduces body fat and improves insulin handling. This method may help the body burn more fat, especially belly fat, compared to daily calorie reduction. Studies have found that this diet combination significantly decreases deep belly fat. Another treatment arm in this trial involves following a Mediterranean diet with daily calorie reduction (MED/DER), which is also effective, particularly when paired with exercise, in lowering body weight, body mass index (BMI), and fat percentage. Both diet plans in this trial aim to improve body composition, but the IER+MED approach might better target belly fat. ^{2 3 4 6 7}

Who Is on the Research Team?

Loic Le Marchand, MD, PhD

Principal Investigator

University of Hawaii Cancer Research Center

Are You a Good Fit for This Trial?

Adults aged 35-69 with a BMI of 25-40 and abdominal obesity (VAT ≥90 cm2 for men, ≥80 cm2 for women), who are non-smokers, drink little alcohol, have no serious health issues or recent substantial weight changes. Must be East Asian, Native Hawaiian/Pacific Islander or White ethnicity and fully vaccinated against COVID-19.

Inclusion Criteria

DXA VAT ≥90 cm2 for men and ≥80 cm2 for women

I have taken antibiotics in the last 3 months.

Fully vaccinated for COVID-19

Exclusion Criteria

I have diabetes and am on insulin treatment.

Contraindication to MR imaging (e.g. pacemaker, claustrophobia, metal implants)

I cannot walk for up to an hour each day.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow either the IER+MED or MED/DER diet plan for 24 weeks, with dietary and physical activity counseling sessions.

24 weeks

4 in-person visits, 12 remote meetings

Follow-up

Participants are monitored for long-term effects on body weight and adiposity, including DXA scans and BMI measurements.

24 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• IER+MED
• MED/DER

Trial Overview The study is testing whether combining Intermittent Energy Restriction (IER) with the Mediterranean diet (MED) is more effective than daily energy restriction (DER) with MED in reducing belly fat and improving cancer-related markers over six months.

How Is the Trial Designed?

Group I: Mediterranean diet (MED) + daily energy restriction (DER) or MED/DER Experimental Treatment 1 Intervention

The MED/DER group intervention will restrict 20% energy (25%, 45% and 30% distribution of protein, carbohydrate, and fat, respectively) continuously. Participants will also be asked to follow a moderate exercise program (1 hour of walking five days a week).

Group II: Intermittent energy restriction (IER) + Mediterranean diet (MED) or IER+MED Experimental Treatment 1 Intervention

The IER+MED group intervention will be to restrict 70% energy (25%, 45% and 30% distribution of protein, carbohydrate, and fat, respectively) on 2 days and follow a MED diet (25%, 45%, 30%) and meet their estimated energy requirement (EER) for the other 5 days each week. This would be equivalent to an over-all 20% daily energy restriction. Participants will also be asked to follow a moderate exercise program (1 hour of walking five days a week).

Who Is Running the Clinical Trial?

University of Hawaii

Lead Sponsor

Trials

122

Recruited

55,200+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

University of Hawaii Cancer Research Center

Collaborator

Trials

11

Recruited

2,100+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Intermittent energy restriction (IER) and continuous energy restriction (CER) both effectively improved metabolic syndrome (MetS) risk factors, but IER showed a significant advantage in increasing HDL cholesterol levels compared to CER.

In terms of secondary outcomes, IER led to greater reductions in body weight, body fat, and fat-free mass compared to CER, indicating that IER may be a more effective approach for weight management in individuals with MetS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent energy restriction vs. continuous energy restriction on cardiometabolic risk factors in patients with metabolic syndrome: a meta-analysis and systematic review. Xu, R., Cao, Y., Wang, PY., et al.[2023]

Intermittent energy restriction (IER) is as effective as continuous energy restriction for weight loss in overweight and obese individuals, with some studies showing greater reductions in body fat and insulin resistance without significant harm.

The long-term effects of IER on health and body composition, especially in normal weight individuals, remain unclear and require further research to determine potential benefits or risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects-A Narrative Review of Human and Animal Evidence. Harvie, M., Howell, A.[2022]

Intermittent energy restriction (IER) and continuous energy restriction resulted in similar weight loss outcomes, with no significant differences in weight loss or body composition after 8-24 weeks across 11 trials.

IER showed a slight reduction in fasting insulin levels, but the clinical significance of this finding is uncertain, indicating that both dietary approaches may be effective for weight management and metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent versus continuous energy restriction on weight loss and cardiometabolic outcomes: a systematic review and meta-analysis of randomized controlled trials. Cioffi, I., Evangelista, A., Ponzo, V., et al.[2020]

In a one-year study involving 332 overweight and obese adults, intermittent energy restriction (IER) methods (week-on-week-off and 5:2) resulted in similar weight loss and body composition changes as continuous energy restriction (CER), with mean weight losses of -6.6 kg for CER, -5.1 kg for week-on-week-off, and -5.0 kg for 5:2.

All three dietary approaches led to improvements in HDL-cholesterol and triglycerides, but there were no significant differences in these outcomes or in fasting glucose and LDL-cholesterol levels among the groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of intermittent compared to continuous energy restriction on weight loss and weight maintenance after 12 months in healthy overweight or obese adults. Headland, ML., Clifton, PM., Keogh, JB.[2021]

A 12-week pilot study involving 60 East Asian participants showed that the Intermittent Energy Restriction combined with a Mediterranean diet (IER+MED) led to significantly greater reductions in visceral adipose tissue (VAT) and total fat mass compared to the DASH diet.

While both diets improved liver function, IER+MED resulted in a more significant decrease in alanine transaminase levels, indicating better liver health, with a low attrition rate of 10% and no major adverse effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Intermittent Energy Restriction Combined with a Mediterranean Diet on Reducing Visceral Adiposity: A Randomized Active Comparator Pilot Study. Panizza, CE., Lim, U., Yonemori, KM., et al.[2023]

Intermittent energy restriction (IER) strategies, such as intermittent fasting and time-restricted feeding, show similar effectiveness in weight loss compared to continuous energy restriction (CER) in adults with obesity, based on a review of randomized trials lasting at least 8 weeks.

Out of 11 studies analyzed, 9 found no significant differences in weight or body fat loss between IER and CER, suggesting that IER can be a viable alternative for obesity treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Intermittent Fasting and Time-Restricted Feeding Compared to Continuous Energy Restriction for Weight Loss. Rynders, CA., Thomas, EA., Zaman, A., et al.[2021]

Intermittent energy restriction (IER) was found to be a feasible and effective weight management strategy for adolescents aged 12-17 with obesity, leading to a significant reduction in BMI %95th percentile after 12 weeks (-5.6%) and maintained reductions at 26 weeks.

Participants reported IER as easy and pleasant to follow, indicating high acceptability, and the intervention also resulted in improvements in cardiovascular health markers, such as reduced carotid intima-media thickness and improved flow-mediated dilation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Energy Restriction Is a Feasible, Effective, and Acceptable Intervention to Treat Adolescents with Obesity. Jebeile, H., Gow, ML., Lister, NB., et al.[2023]

Intermittent energy restriction (IER) led to significant weight loss in overweight and obese adults, averaging about 0.2-0.8 kg per week, and was found to be as effective as daily energy restriction (DER) when total energy intake was similar.

Most studies indicated that IER was equally effective as DER in reducing fat mass, fat-free mass, and waist circumference, suggesting it could be a viable alternative weight-loss strategy for health practitioners.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent energy restriction and weight loss: a systematic review. Davis, CS., Clarke, RE., Coulter, SN., et al.[2022]

Intermittent energy restriction, which includes methods like alternate day fasting, was found to be more effective than no treatment for weight loss in overweight and obese adults, with an average loss of 4.14 kg over the study period.

However, when compared to continuous energy restriction, intermittent energy restriction did not show a significant difference in weight loss, indicating that both approaches may be similarly effective for short-term weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis. Harris, L., Hamilton, S., Azevedo, LB., et al.[2022]

Intermittent energy restriction (IER) diets, such as alternate-day fasting and time-restricted feeding, are effective for weight loss and can improve metabolic health markers like blood pressure, lipid levels, and glucose control.

IER diets are as effective as continuous energy restriction diets for weight loss, making them a viable alternative for individuals who struggle with constant calorie restriction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Intermittent Energy Restriction Diet on Metabolic Profile and Weight Loss among Obese Adults. Stanek, A., Brożyna-Tkaczyk, K., Zolghadri, S., et al.[2022]

In a 2-week study with 16 healthy-weight participants, both intermittent energy restriction (IER) and continuous energy restriction (CER) resulted in similar weight loss, around 2.5 kg, indicating that IER can be as effective as CER for weight reduction.

While there were no significant differences in post-meal insulin or blood glucose levels between the two diets, IER led to lower fasting blood glucose levels and improved appetite ratings, suggesting potential metabolic benefits of IER beyond just weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of intermittent (5:2) or continuous energy restriction on basal and postprandial metabolism: a randomised study in normal-weight, young participants. Gao, Y., Tsintzas, K., Macdonald, IA., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31226790/

Effects of Intermittent Energy Restriction Combined with a ... Intermittent energy restriction combined with a Mediterranean diet (IER+MED) has shown promise to reduce body fat and insulin resistance.

2. t.uhcancercenter.org t.uhcancercenter.org/pdf/quest/s1/2019%20Panizza%20Nutrients19%20IER+MED%20vs%20DASH%20on%20visceral%20fat.pdf

Effects of Intermittent Energy Restriction Combined with a ... Abstract: Intermittent energy restriction combined with a Mediterranean diet (IER+MED) has shown promise to reduce body fat and insulin ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05132686

NCT05132686 | The Healthy Diet and Lifestyle Study II IER has been proposed to invoke a greater metabolic shift to fat metabolism than DER and preferentially reduce central obesity. The Investigators adapted the ...

4. researchgate.net researchgate.net/publication/333912688_Effects_of_Intermittent_Energy_Restriction_Combined_with_a_Mediterranean_Diet_on_Reducing_Visceral_Adiposity_A_Randomized_Active_Comparator_Pilot_Study

(PDF) Effects of Intermittent Energy Restriction Combined ... Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol,. Protein, Amino Acids (Macronutrients), 2nd ed.; ...

5. mdpi.com mdpi.com/2072-6643/16/10/1478

Protocol for The Healthy Diet and Lifestyle Study 2 (HDLS2) ... MED, encompassing equivalent overall energy restrictions and analogous dietary compositions, on visceral and liver fat reduction. Primary ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6627434/

Effects of Intermittent Energy Restriction Combined with a ... ... diet (IER+MED) has shown promise to reduce body fat ... energy restriction, Mediterranean diet, randomized trial, total adiposity, visceral adipose tissue ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04526847

Intermittent Fasting Compared to Continuous Energy ... They will receive a diet plan that recommended ~50 gm protein/day from chicken breast, lean meat, lean fish, fat-free yogurt, cottage cheese, egg or legumes, ...