An interventional study of Fructose Solution (75 Grams) and Glucose Solution (75 grams) in Non-Alcoholic Fatty Liver Disease and Obesity, sponsored by Rockefeller University. Completed at 1 site in United States. Open to participants aged 45 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-03-26.
Sponsored by Rockefeller University · Not applicable, Interventional, and Basic science
Non alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver function tests in the U.S. (Browning, et al., 2004), ranging from steatosis to end-stage liver disease. Fructose ingestion by the American public has steadily increased since the 1980's, and with it increases in NAFLD, fatty liver hepatitis (NASH), diabetes, obesity, and cardiovascular disease. Foods and beverage in the U.S. are typically sweetened with sucrose (50% glucose and 50% fructose) or high fructose corn syrup (45-58% glucose and 42-55% fructose) (Stanhope, et al., 2009). Research into the role that added fructose plays in the emerging chronic health issues is necessary to affect public policy and provide the connection between fructose and the increasing incidence of these co-morbidities.
There is evidence that gut bacteria contribute to a range of human diseases including those of the liver and gastrointestinal tract. Dietary fructose has been suggested to play a role in the development of these diseases and has been shown to alter gut microbes in animals. If the investigators find that dietary fructose alters bacteria in the human gut, this would suggest a potential targetable link between high fructose diet and disease.
Non- alcoholic fatty liver disease (NAFLD) occurs in 30% of the adult US population (Luther, J., et al., 2015). Eating large amounts of fructose (a dietary sugar) increases liver fat accumulation and worsens NAFLD. In addition, fructose consumption has been shown to greatly increase triglycerides(fat) in the blood after meals, increasing the risk of heart disease,(Stanhope,et al., 2009) insulin resistance and diabetes. Current theories on liver disease caused by consuming fructose focuses on changes in the breakdown of fat by the liver. In experimental animals, fructose feeding changes the bacteria population (microbiota) in the gut, causes NAFLD and NASH, and increases leaking of toxins from the intestine (intestinal permeability) to the blood stream resulting in inflammation.
In humans, fructose consumption rapidly increases liver fat. However, changes in gut microbiota have not been studied. The proposed study will compare the addition of fructose or glucose to the study subjects' usual diet in a crossover design. They will not know which sugar they are receiving.
The Investigators plan to study postmenopausal, moderately obese but healthy women, and moderately obese but healthy men (age 45-70 years) to find out the effect of fructose verses glucose on the bacteria in their stool and inflammation in the bowel. The Investigators hypothesize that adding fructose to the participant's usual diet, compared to glucose, will change stool bacteria composition and the products that the bacteria produce, which may increase intestinal leakage, and increase markers of inflammation in the stool and blood due to this leakage. These changes may contribute to fructose -induced liver disease.
Exclusion Criteria:
Participants first receive Glucose Solution (75 grams) from Day 3 through Day 16 of an inpatient stay with usual diet. After a 2-3 week washout period, they will then receive Fructose Solution (75 Grams) from Day 3 through Day 16 on a second inpatient stay with usual diet.
Other: Fructose Solution (75 Grams) · Other: Glucose Solution (75 grams)
Participants first receive Fructose Solution (75 grams) from Day 3 through Day 16 of an inpatient stay with usual diet. After a 2-3 week washout period, they will then receive Glucose Solution (75 grams) from Day 3 through Day 16 on a second inpatient stay with usual diet.
Other: Fructose Solution (75 Grams) · Other: Glucose Solution (75 grams)
Fructose given in divided doses at breakfast and dinner.
Glucose given in divided doses at breakfast and dinner.
Also known as: Dextrose
Difference in the Distribution of Fecal Microbiota in Each Participant
Difference in the distribution of fecal microbiota in each participant, between the fructose versus glucose supplemented diet arms of the study, as measured at the end of each intervention.
Time frame: assessed at Day 16 of each intervention, up to 64 days
| Milestone | Fructose, Then Glucose | Glucose, Then Fructose |
|---|---|---|
| Started | 6 | 7 |
| Completed | 4 | 6 |
| Not completed | 2 | 1 |
| Withdrew: Adverse event | 1 | 1 |
| Withdrew: Withdrawal by subject | 1 | 0 |
Difference in the distribution of fecal microbiota in each participant, between the fructose versus glucose supplemented diet arms of the study, as measured at the end of each intervention.
No measurements were reported for this outcome.
Collected over 10 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Fructose, Then Glucose | 0/4 (0%) | 0/4 (0%) | 3/4 (75%) |
| Glucose, Then Fructose | 0/6 (0%) | 0/6 (0%) | 3/6 (50%) |
| Event | Fructose, Then Glucose | Glucose, Then Fructose |
|---|---|---|
| BloatingGastrointestinal disorders | 2/4 | 3/6 |
| nauseaGastrointestinal disorders | 1/4 | 0/6 |
| elevated blood glucoseMetabolism and nutrition disorders | 1/4 | 1/6 |
| lightheadednessNervous system disorders | 1/4 | 0/6 |
| low back painMusculoskeletal and connective tissue disorders | 0/4 | 1/6 |
Glucose to Fructose group, 1 was withdrawn due to A/E Total evaluated = 6 Fructose to Glucose group: 1 was withdrawn due to A/E, 1 due to personal reason Total evaluated = 4
| Age, Categorical(Participants) | Glucose, Then Fructose | Fructose, Then Glucose | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 6 | 4 | 10 |
| >=65 years | 1 | 2 | 3 |
| Age, Continuous(years) | Glucose, Then Fructose | Fructose, Then Glucose | Total |
|---|---|---|---|
| Mean | 58 (50 to 67) | 57 (52 to 65) | 57.6 (50 to 67) |
| Sex: Female, Male(Participants) | Glucose, Then Fructose | Fructose, Then Glucose | Total |
|---|---|---|---|
| Female | 3 | 3 | 6 |
| Male | 4 | 3 | 7 |
| Ethnicity (NIH/OMB)(Participants) | Glucose, Then Fructose | Fructose, Then Glucose | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 1 | 2 |
| Not Hispanic or Latino | 6 | 5 | 11 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Glucose, Then Fructose | Fructose, Then Glucose | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 5 | 4 | 9 |
| White | 2 | 2 | 4 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Glucose, Then Fructose | Fructose, Then Glucose | Total |
|---|---|---|---|
| United States | 7 | 6 | 13 |
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Rockefeller University