Fructose Intake for Healthy Subjects

Overseen By Mark Herman, MD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Must not be taking: Any medications

Disqualifiers: Significant illness, Fructose intolerance, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications except oral contraceptives to participate in this trial.

What data supports the effectiveness of fructose ingestion as a treatment for healthy subjects?

Research suggests that small doses of fructose may help improve blood sugar control, as they have been shown to reduce blood sugar levels after meals in some studies. However, the evidence is not very strong, and more research is needed to confirm these findings. ^{1 2 3 4 5}

Is fructose safe for human consumption?

Recent studies suggest that consuming fructose in normal dietary amounts does not lead to adverse health effects. However, high intake of fructose may affect lipid levels and glucose metabolism differently than glucose, so moderation is advised. ^{6 7 8 9 10}

How does fructose ingestion differ from other treatments for healthy subjects?

Fructose ingestion is unique because it is absorbed differently than glucose, with fructose being more readily taken up when combined with glucose. This treatment focuses on understanding how fructose and glucose affect metabolism and absorption, which is different from other treatments that might not consider these specific interactions. ^{1 2 3 10 11}

What is the purpose of this trial?

The goal of this clinical trial is to learn how fructose ingestion affects metabolic factors in healthy adults aged 18-64, with a BMI between 19 and 30 kg/m², of any sex or gender. Specifically, the study aims to examine the impact of fructose compared to glucose on circulating metabolic factors including the soluble leptin receptor. The main questions it aims to answer are: How does fructose ingestion influence levels of circulating metabolic markers, including the soluble leptin receptor? Does fructose consumption have different metabolic effects compared to glucose? Participants will: Complete a screening phone call to review their health history and eligibility. Attend two in-person visits at least two weeks apart, where they will: Fast for 8 hours beforehand. Consume a beverage containing either 75g of fructose or glucose. Have blood drawn at regular intervals for up to 5 hours after consumption to measure circulating levels of metabolic markers.

Eligibility Criteria

This trial is for healthy adults aged 18-64 with a BMI of 19-30 kg/m². Participants must be willing to fast, consume beverages with fructose or glucose, and have their blood drawn regularly during two separate visits.

Inclusion Criteria

BMI: Participants must have a Body Mass Index (BMI) between 19 and 30 kg/m² (healthy weight to slightly overweight)

I am either male or female.

I am a healthy volunteer without significant medical conditions.

Exclusion Criteria

I am only taking oral contraceptives, no other medications.

Known significant medical illness

History of fructose intolerance

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (phone call)

Treatment

Participants consume a beverage containing either 75g of fructose or glucose and have blood drawn at regular intervals for up to 5 hours

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for changes in metabolic markers after treatment

4 weeks

Treatment Details

Interventions

• Fructose Ingestion
• Glucose Ingestion

Trial Overview The study compares the metabolic effects of fructose versus glucose ingestion in healthy individuals. It focuses on how these sugars influence circulating metabolic markers like the soluble leptin receptor after consumption.

Participant Groups

Group I: Glucose First, Fructose Second (10 participants) Experimental Treatment 2 Interventions

Participants will first consume 75g of glucose in 225ml of water, followed by the same blood sampling schedule. After 2 weeks, they will switch to 75g of fructose, with blood samples taken at the same intervals.

Group II: Fructose First, Glucose Second (10 participants) Experimental Treatment 2 Interventions

Participants will first consume 75g of fructose in 225ml of water. Blood samples will be taken at specific intervals to measure metabolic responses. After 2 weeks, they will consume 75g of glucose in 225ml of water, with blood samples taken at the same intervals.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Findings from Research

In a study involving 10 healthy adults, fructose absorption varied significantly, with some individuals able to absorb over 50 g, while one subject showed malabsorption at just 10 g, indicating a wide range of individual responses to fructose.

The presence of glucose alongside fructose improved absorption, suggesting that glucose enhances fructose uptake, and highlighting the potential for different intestinal transport mechanisms for fructose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absorption capacity of fructose in healthy adults. Comparison with sucrose and its constituent monosaccharides. Rumessen, JJ., Gudmand-Høyer, E.[2022]

The study indicates that intestinal transport of d-allulose is mediated by the glucose transporter type 5 (GLUT5), particularly enhanced in rats fed fructose, which increased GLUT5 expression.

When d-allulose is consumed with d-fructose, its absorption is reduced, suggesting that d-fructose competes with d-allulose for transport via GLUT5, indicating that d-allulose has a lower affinity for this transporter compared to d-fructose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

d-Allulose is a substrate of glucose transporter type 5 (GLUT5) in the small intestine. Kishida, K., Martinez, G., Iida, T., et al.[2020]

In a study involving 24 participants with type 2 diabetes, allulose significantly reduced postprandial blood glucose levels by 8% at a dose of 10 g compared to a control, indicating its potential as a beneficial sweetener for blood sugar management.

Fructose did not show any effect on blood glucose levels at any dose, highlighting that allulose may be a more effective option for individuals with type 2 diabetes in regulating post-meal glucose spikes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of small doses of fructose and allulose on postprandial glucose metabolism in type 2 diabetes: A double-blind, randomized, controlled, acute feeding, equivalence trial. Noronha, JC., Braunstein, CR., Glenn, AJ., et al.[2023]

D-psicose is rapidly absorbed into the bloodstream after oral administration, reaching peak concentration within 1 hour, and is primarily eliminated through urine, with 20% excretion within 1 hour and 33% within 2 hours.

The study found that D-psicose accumulates only in the liver and not in the brain, indicating a specific organ distribution, and highlights the need for human trials to better understand its metabolism and potential applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal absorption, organ distribution, and urinary excretion of the rare sugar D-psicose. Tsukamoto, I., Hossain, A., Yamaguchi, F., et al.[2018]

Small doses of fructose (≤10 g/meal) and tagatose have been shown to significantly reduce HbA1c and fasting glucose levels in individuals with and without diabetes, suggesting potential long-term benefits for glycemic control.

The evidence for the effectiveness of tagatose is considered moderate, while the evidence for fructose and allulose is graded as low, indicating a need for more long-term studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Small Doses of Fructose and Its Epimers on Glycemic Control: A Systematic Review and Meta-Analysis of Controlled Feeding Trials. Noronha, JC., Braunstein, CR., Blanco Mejia, S., et al.[2022]

Adult rats can effectively absorb small amounts of fructose (0.4 g), but higher doses (greater than 0.6 g) lead to acute malabsorption, indicating a threshold for effective absorption.

The presence of glucose or galactose significantly enhances fructose absorption, especially when consumed together in equal amounts, while sucrose and certain inhibitors can reduce this absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal absorption of fructose in the rat. Fujisawa, T., Riby, J., Kretchmer, N.[2019]

A 90-day toxicity test on rats showed that D-allulose, produced from a non-GMO source, has a No Observed Adverse Effect Level (NOAEL) of 5,000 mg/kg/day, indicating it is safe for consumption at this level.

The study found only minor changes in health indicators at high doses, supporting the classification of D-allulose as a safe and ordinary substitute for sucrose with 70% of its sweetness and ultra-low energy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

90-Day repeated oral toxicity test of D-allulose produced from Microbacterium foliorum. An, M., Lee, J., Park, YC., et al.[2020]

In a study involving healthy subjects, cellobiose was found to be safe and well-tolerated, with a maximum tolerated dose identified as 20 g for single use and 15 g twice daily for repeated consumption.

Despite some mild gastrointestinal side effects like flatulence and transient diarrhea in sensitive individuals, the overall tolerability rating was high, indicating that cellobiose could be a beneficial low-caloric bulking agent in food products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Dose-Escalation Study Demonstrates the Safety and Tolerability of Cellobiose in Healthy Subjects. Moré, MI., Postrach, E., Bothe, G., et al.[2020]

Recent randomized controlled trials (RCTs) indicate that consuming fructose, high fructose corn syrup (HFCS), and sucrose at normal dietary levels does not show significant adverse health effects, challenging common concerns about these sugars.

The review emphasizes the need for caution in making health claims about these sugars, as most studies have compared pure forms of sugars rather than how they are typically consumed in diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The metabolic and endocrine response and health implications of consuming sugar-sweetened beverages: findings from recent randomized controlled trials. Rippe, JM.[2023]

Dietary fructose significantly increases fasting triglycerides and LDL cholesterol levels compared to glucose, which does not have these effects, highlighting the different metabolic impacts of these sugars over a 4- to 6-week period.

In free-living conditions, adding moderate amounts of fructose to the diet (30-60 g) did not significantly affect lipid or glucose biomarkers, suggesting that the context of sugar intake matters for metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary fructose and glucose differentially affect lipid and glucose homeostasis. Schaefer, EJ., Gleason, JA., Dansinger, ML.[2023]

The study suggests that the differences in how fructose and glucose affect food intake are influenced more by factors like timing and volume of consumption rather than inherent differences in their ability to induce feelings of fullness.

Overall, there is insufficient evidence to support the idea that fructose or high-fructose corn syrup is less satiating than glucose or sucrose, indicating that their roles in the obesity epidemic may not be as straightforward as previously thought.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fructose and satiety. Moran, TH.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Absorption capacity of fructose in healthy adults. Comparison with sucrose and its constituent monosaccharides. [2022]

2. England pubmed.ncbi.nlm.nih.gov

d-Allulose is a substrate of glucose transporter type 5 (GLUT5) in the small intestine. [2020]

3. England pubmed.ncbi.nlm.nih.gov

The effect of small doses of fructose and allulose on postprandial glucose metabolism in type 2 diabetes: A double-blind, randomized, controlled, acute feeding, equivalence trial. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Intestinal absorption, organ distribution, and urinary excretion of the rare sugar D-psicose. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The Effect of Small Doses of Fructose and Its Epimers on Glycemic Control: A Systematic Review and Meta-Analysis of Controlled Feeding Trials. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Intestinal absorption of fructose in the rat. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

90-Day repeated oral toxicity test of D-allulose produced from Microbacterium foliorum. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

A Dose-Escalation Study Demonstrates the Safety and Tolerability of Cellobiose in Healthy Subjects. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

The metabolic and endocrine response and health implications of consuming sugar-sweetened beverages: findings from recent randomized controlled trials. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Dietary fructose and glucose differentially affect lipid and glucose homeostasis. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Fructose and satiety. [2023]