High Fructose Diet for Obesity

Overseen By Ryan Walker

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Probiotics, Antibiotics, others

Disqualifiers: Diabetes, Eating disorders, others

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

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a diet high in fructose, a type of sugar, affects gut health and its connection to metabolic issues like insulin resistance and type 2 diabetes. Participants will follow a special diet that includes either high fructose or high glucose meals for a set period to observe the effects on the gut microbiome (the community of microbes in the intestines) and overall metabolic health. The trial aims to uncover how changes in the gut caused by fructose might increase the risk of metabolic diseases. The study seeks individuals who have trouble absorbing fructose (fructose malabsorbers), identifiable through a specific breath test. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on diet and metabolic health.

Will I have to stop taking my current medications?

The trial excludes participants who are on chronic medications that affect body weight, insulin resistance, or lipid profiles. If you are taking such medications, you may need to stop them to participate in the trial.

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

Research has shown that consuming high amounts of fructose, a type of sugar, can impact health in various ways. One study found that women on a high fructose diet had lower blood sugar but higher triglyceride levels, which could increase heart disease risk. Another study discovered that high fructose intake can lead to increased liver fat and insulin issues, linked to diabetes and other health problems.

These studies suggest potential risks, but not everyone will experience these issues. Those considering a trial involving a high fructose diet should be aware of possible changes in blood fat levels and liver health. Consulting a healthcare provider is advisable for any concerns about this type of diet. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the high fructose diet for obesity because it explores a unique dietary approach rather than conventional treatments like lifestyle changes, medications, or surgery. Unlike typical methods that often focus on reducing calorie intake or increasing calorie burn, this study examines the effects of specific types of sugars—fructose and glucose—on weight maintenance. By alternating between high fructose and high glucose diets, researchers hope to uncover how these sugars might differently impact weight and metabolism, potentially paving the way for more targeted dietary strategies for managing obesity.

What evidence suggests that this trial's treatments could be effective for metabolic health?

Research has shown that consuming a lot of fructose, a type of sugar, links to health problems. Studies have found that fructose can impair the body's ability to control sugar levels, increasing the risk of type 2 diabetes. In animal studies, diets high in fructose led to fat buildup in the liver and higher blood fat levels, both associated with obesity and other health issues. Although evidence in humans is less clear, it suggests that excessive fructose intake can cause similar problems, such as poor liver function and unhealthy blood fat levels. This trial will compare the effects of a high fructose diet with a high glucose diet on these health markers. These findings highlight the potential negative effects of consuming too much fructose. ^{1 4 5 6 7}

Who Is on the Research Team?

Ryan Walker

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for adults with Type 2 Diabetes, Mesenteric Artery Stenosis, or Obesity. Participants will be tested on how a high fructose diet versus a glucose diet affects their gut microbiome and metabolic health. They should not have conditions that interfere with the study's dietary requirements.

Inclusion Criteria

Participants must be determined to be a fructose malabsorber via hydrogen breath test

Exclusion Criteria

Consumption of > 1 sugar sweetened beverage per day

Use of probiotic/prebiotic/synbiotic supplements

Vegetarian, vegan or other restrictive dietary habits

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dietary Intervention

Participants consume a 12-day isocaloric high fructose diet followed by a 12-day isocaloric high glucose diet, with a 10-day washout period in between

34 days

Follow-up

Participants are monitored for safety and effectiveness after the dietary intervention

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• High Fructose Diet

Trial Overview

The study tests the effects of a controlled high fructose diet compared to a glucose diet on participants' gut bacteria and metabolism. It involves consuming specific diets for 12 days, followed by a washout period, then switching diets. The impact on liver fat and diabetes risk markers will also be studied using advanced techniques like MRI elastography.

How Is the Trial Designed?

Group I: Glucose Dietary then Fructose Dietary Experimental Treatment 2 Interventions

Participants that will be randomized to the 12-day isocaloric weight-maintaining high glucose diet, then will change to the12-day isocaloric weight-maintaining high fructose diet after a 10-day washout period.

Group II: Fructose Dietary then Glucose Dietary Experimental Treatment 2 Interventions

Participants that will be randomized to the 12-day isocaloric weight-maintaining high fructose diet, then will change to the 12-day isocaloric weight-maintaining high glucose diet after a 10-day washout period.

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Metabolic Solutions Inc.

Industry Sponsor

Trials

5

Recruited

180+

Published Research Related to This Trial

In a study of 131 obese patients over 6 weeks, a moderate natural fructose diet led to greater weight loss (4.19 kg) compared to a low-fructose diet (2.83 kg), suggesting that not all fructose is equally harmful.

Both diets resulted in significant improvements in metabolic syndrome parameters, indicating that reducing energy and added fructose intake can be an effective strategy for combating obesity and diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of two energy-restricted diets, a low-fructose diet versus a moderate natural fructose diet, on weight loss and metabolic syndrome parameters: a randomized controlled trial. Madero, M., Arriaga, JC., Jalal, D., et al.[2017]

In a review of 31 isocaloric trials with 637 participants, fructose did not significantly affect body weight when substituted for other carbohydrates in diets with the same calorie content.

However, in 10 hypercaloric trials with 119 participants, high doses of fructose (providing excess calories) led to modest weight gain, suggesting that the increase in weight may be due to the extra calories rather than fructose itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of fructose on body weight in controlled feeding trials: a systematic review and meta-analysis. Sievenpiper, JL., de Souza, RJ., Mirrahimi, A., et al.[2022]

In a study involving 17 monkeys on a high-fructose diet for up to 7 years, those allowed to eat freely developed hepatic steatosis (HS) and increased diabetes incidence, indicating that long-term fructose consumption can lead to significant liver fat accumulation and metabolic issues.

Even without weight gain, monkeys on a controlled high-fructose diet for 6 weeks showed liver damage and increased markers of endotoxemia and microbial translocation, suggesting that fructose can harm liver health rapidly through mechanisms unrelated to obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary fructose induces endotoxemia and hepatic injury in calorically controlled primates. Kavanagh, K., Wylie, AT., Tucker, KL., et al.[2023]

Chronic consumption of a high-fructose diet in Sprague-Dawley rats led to leptin resistance, which means that the rats' bodies became less responsive to leptin, a hormone that helps regulate hunger and energy balance.

This leptin resistance occurred before any significant weight gain or changes in fat levels, and when these fructose-fed rats were later given a high-fat diet, they gained significantly more weight compared to rats that had not been exposed to fructose, highlighting a potential mechanism linking fructose intake to obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding. Shapiro, A., Mu, W., Roncal, C., et al.[2021]

In a study involving mice fed a high-fructose diet for 6 weeks, protodioscin significantly improved glucose intolerance and reduced harmful serum levels of uric acid, blood urea nitrogen, creatinine, total cholesterol, and triglycerides.

Protodioscin also showed protective effects on kidney health by reducing inflammation markers and improving kidney tissue damage, suggesting it could be a promising treatment for metabolic syndrome and renal injury caused by high fructose intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protodioscin ameliorates fructose-induced renal injury via inhibition of the mitogen activated protein kinase pathway. Shen, J., Yang, X., Meng, Z., et al.[2018]

Excessive consumption of fructose, particularly in amounts that exceed 25-40% of total caloric intake, is linked to weight gain, increased triglyceride levels, and fatty liver disease, as shown in meta-analyses of studies lasting from one to ten weeks.

The effects of high fructose intake cannot be separated from overall excessive caloric intake, indicating that more high-quality randomized controlled trials are needed to understand fructose's specific metabolic impacts, especially in children who are particularly vulnerable to high sugar consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fructose Consumption-Free Sugars and Their Health Effects. Stricker, S., Rudloff, S., Geier, A., et al.[2021]

Fructose consumption is linked to obesity and metabolic syndrome, which can increase the risk of developing diabetes, highlighting its potential negative health impacts.

The review discusses how fructose contributes to fatty liver, obesity, and insulin resistance, emphasizing the metabolic changes induced by high fructose corn syrup and dietary fructose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mini review on fructose metabolism. Akram, M., Hamid, A.[2013]

A systematic review found no evidence that normal dietary intake of fructose leads to increased triglycerides or body weight in overweight or obese individuals.

Previous studies linking fructose consumption to hyperlipidemia or obesity may not apply to overweight or obese populations due to their unique metabolic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based review on the effect of normal dietary consumption of fructose on blood lipids and body weight of overweight and obese individuals. Dolan, LC., Potter, SM., Burdock, GA.[2019]

Excessive consumption of fructose, particularly from added sugars, is linked to negative health outcomes such as increased visceral fat, lipid dysregulation, and reduced insulin sensitivity, raising the risk for cardiovascular disease and type 2 diabetes.

Current dietary guidelines recommend limiting sugar intake, but more research is needed to understand the specific adverse effects of fructose compared to other sugars like glucose, especially through dose-response studies in both normal and overweight individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fructose consumption: recent results and their potential implications. Stanhope, KL., Havel, PJ.[2021]

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