Alcohol Use Disorder
Conditions
Keywords
Inflammation, Leaky gut, Supplements
Brief summary
Chronic alcohol consumption leads to perturbations in gut microbiome balance (dysbiosis) and disruption of gut barrier integrity. As a result, bacteria, toxins, and metabolites can enter the blood stream and reach distant organs, triggering inflammation and oxidative stress. Through this mechanism gut leak is closely related to the onset of metabolic diseases, such as nonalcoholic fatty liver disease (NAFLD) and diabetes. Despite the prominent role of diet and alcohol in the pathogenesis of metabolic diseases, there is a lack of treatments to mitigate their effects in triggering systemic inflammation and oxidative stress. Novel treatments using generally recognized as safe (GRAS) compounds focused on restoring the intestinal barrier to mitigate metabolite endotoxemia are sorely needed. This project will test the potential of broccoli sprouts extract (BSE) as a GRAS treatment to minimize the combined effect of poor nutrition and alcohol on the gut. Broccoli sprouts are rich in sulforaphane, a bioactive compound derived from the glucosinolate glucoraphanin with anti-inflammatory and antioxidant proprieties. BSE supplementation has been used in preclinical and clinical studies as a health- promoting food, showing significant positive changes in the gut microbiota composition, protection against colitis, cardiometabolic improvement, and lower inflammation. We believe that BSE is a viable alternative therapeutic approach for patients who are resistant to lifestyle changes such as healthy eating and reducing alcohol use. Our purpose is to test BSE supplementation in human subjects with poor nutrition compounded by alcohol use, specifically in older adults who we believe will receive greater benefit from this approach. At the completion of the proposed study, we expect to have determined that treatments using generally recognized as safe (GRAS) compounds can be useful to restore the gut barrier integrity, and as consequence of reduced gut leak we expect to observe lower inflammation and oxidative stress.
Interventions
DIETARY_SUPPLEMENTGenerally Recognized as Safe - Sulforaphane
Participants will be asked to maintain the same food ingestion habits as before the study and take 2 tablets of Sulforaphane a day with a meal for 28 days.
DIETARY_SUPPLEMENTPlacebo
Participants will be asked to maintain the same food ingestion habits as before the study and take 2 tablets of placebo a day with a meal for 28 days.
Sponsors
Louisiana State University Health Sciences Center in New Orleans
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Labels of the product will be replaced with "Tablets A" and "Tablets B" labels.
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects ≥ 50 years of age at enrollment. * Consume at least 8 alcoholic drinks/week. AUDIT-C score \>8.
Exclusion criteria
* Bowel-related diseases * Diagnosed Diabetes * Allergy or intolerance to broccoli. * Any acute illness within the last 6 weeks. * Chronic anti-inflammatory use or antibiotic treatment in the last 7 days. * Acute illness within the preceding six weeks (defined as fever, new antibiotic use or unscheduled healthcare visit - for illness). * Acute alcohol intoxication upon arrival on the day of study visit. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gut Leak | Serum concentration of intestinal fatty acid-binding protein and LPS biding protein at 28 days. | Measured by serum levels of intestine fatty acid biding proteins and LPS biding protein. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biomarkers of Inflammation | After 28 days of treatment | Interleukin-6 (IL-6) and Interleukin-1 beta (IL-1β) are proteins in the blood that help control the body's immune and inflammatory responses. They are released when the body is reacting to stress, infection, or injury. Higher levels of these markers generally indicate increased inflammation in the body and are commonly used to assess overall immune system activity. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAline Zaparte, PhD
Postdoctoral Fellow
Participant flow
Recruitment details
Participants were recruited through the distribution of flyers.
Pre-assignment details
No participants were excluded before assignment. 40 participants initiated the study but only 38 completed the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 60.23 Years STANDARD_DEVIATION 6.05 |
| GSH/GSSG redox ratio | 0.57 Ratio STANDARD_DEVIATION 0.16 |
| Interleukin-1 beta (IL-1β) | 6.97 pg/mL STANDARD_DEVIATION 0.77 |
| Interleukin-6 | 4.61 pg/mL STANDARD_DEVIATION 2.9 |
| Intestine Acid Fatty Biding Protein | 2.66 μg/mL STANDARD_DEVIATION 1.46 |
| LPS Biding Protein | 27.33 µg/mL STANDARD_DEVIATION 8.28 |
| Malondialdehyde (MDA) | 0.200 µM/mL STANDARD_DEVIATION 0.12 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 11 Participants |
| Total Antioxidant Capacity (TAC) | 80.05 µM STANDARD_DEVIATION 16.79 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
None listed