Pomegranate Dietary Supplements in AUD and ALD
Supplementation of Pomegranate Dietary Supplements and Characterization of Urolithin Metabotypes in Patients With Alcohol Use Disorder (AUD) and Alcohol-associated Liver Disease (ALD)
Studieoversikt
Status
Intervensjon / Behandling
Detaljert beskrivelse
A large body of anecdotal evidence suggests beneficial effects for many botanical dietary supplements (BDS) on human health. The U.S. alone spent ~$7.5 billion on BDS in 2016, suggesting significant interest in the consumption of such products. Since ancient times, pomegranate has been known as a 'healing food', with numerous health benefits, including prevention of health risk factors for high blood pressure, arthritis, high cholesterol, oxidative stress, and hyperglycemia (1-4). Despite reported benefits from consumption of pomegranate dietary supplements (PDS), the overall outcomes of clinical trials were not uniform, and the results were inconclusive (5-7). However, gut microbial metabolites derived from polyphenolics of pomegranate have been shown to promote many beneficial activities, including anti-oxidative and anti-inflammatory activities (8- 12). Thus, the inter-individual variation in human gut microbiota compositions and their metabolic capacities may hamper the predicted PDS-mediated benefits. We postulate that harboring the specific gut microbiota responsible for metabolizing PDS into beneficial metabolites is critical to manifesting the complete benefits of PDS consumption. Recently, we reported one such microbial metabolite, 'urolithin A' (UroA), derived from ellagic acid-rich diets (e.g., pomegranate), significantly enhanced gut barrier function in addition to blocking unwarranted inflammation in colitis models (13) and protected from alcoholic liver disease (ALD) in mouse models (unpublished data). UroA is produced only in 40-50% of humans, who harbor the appropriate microbiota capable of converting consumed ellagic acid-rich diets (such as pomegranates, berries, and walnuts). UroA levels varied significantly among populations, to micromolar levels in some individuals. The direct correlations between UroA levels and human health/disease conditions are not yet available.
This project aims to determine an individual's ability to generate active gut microbial metabolites called urolithins upon consumption of pomegranate dietary supplements. We, and others, reported that urolithins are the major active metabolites that are responsible for the beneficial activities that are rendered from eating pomegranates, berries, or walnuts. However, the production of urolithins from the parent compound ellagic acid (EA) is dependent upon the presence of certain bacteria in the human gut. In this trial, we propose to investigate variations in gut microbiota and their capacity to metabolize pomegranate dietary supplements (PDS) into active urolithins. We will measure the levels of urolithins in blood as well as inflammatory cytokines in plasma samples upon consumption of PDS.
Studietype
Registrering (Antatt)
Kontakter og plasseringer
Studiekontakt
- Navn: Vatsalya Vatsalya, MD
- Telefonnummer: 502-852-8928
- E-post: v0vats01@louisville.edu
Studer Kontakt Backup
- Navn: Venkatakrishna R Jala, PhD
- Telefonnummer: 502-852-5523
- E-post: jvrao001@louisville.edu
Studiesteder
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Kentucky
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Louisville, Kentucky, Forente stater, 40202
- University of Louisville
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Hovedetterforsker:
- Craig J McClain, M.D.
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Hovedetterforsker:
- Vatsalya Vatsalya, M.D.
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Hovedetterforsker:
- Ventakrishna R Jala, Ph.D.
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Ta kontakt med:
- Vatsalya Vatsalya, M.D.
- Telefonnummer: 502-852-8928
- E-post: v0vats01@louisville.edu
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Ta kontakt med:
- Steve Mahanes, M.S.
- Telefonnummer: 502-852-1388
- E-post: steve.mahanes@louisville.edu
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Prøvetakingsmetode
Studiepopulasjon
Beskrivelse
Healthy Group:
Inclusion: Healthy individuals, Exclusion: AUD, ALD, AC, and inflammatory conditions,
Alcohol Use Disorder Group:
Inclusion: AUD diagnosis Exclusion: alcohol-associated systemic conditions
Alcohol-associated liver disease Group:
Inclusion: early-stage ALD comorbid with AUD Exclusion: Only AUD or AUD with AC
Alcohol-associated cirrhosis Inclusion: AC with AUD Exclusion: AUD, and early stage ALD, as well as determined by the study cohort criteria
Studieplan
Hvordan er studiet utformet?
Designdetaljer
Kohorter og intervensjoner
Gruppe / Kohort |
Intervensjon / Behandling |
|---|---|
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healthy volunteers
Adults ≥18, Drink no alcohol or drink < 50 grams of alcohol per day on average if female and < 80 grams per day on average if male; 3 capsules of the PDS (pomegranate dietary supplement - Nutricost Pomegranate Extract) - dose of 400 mg
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Nutricost Pomegranate Extract 15,000mg Equivalent from 1,000mg of 15:1 Extract Per Servings, 120 Capsules for 40 Servings Per Bottle - Vegan, GMO Free and Gluten Free;
Andre navn:
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Alcohol Use Disorder (AUD) subjects
Adults ≥18; Must consume >20 standardized alcoholic beverages a week for the last 3 months for men, >14 standard alcoholic beverages a week for women; 3 capsules of the PDS (pomegranate dietary supplement - Nutricost Pomegranate Extract) - dose of 400 mg
|
Nutricost Pomegranate Extract 15,000mg Equivalent from 1,000mg of 15:1 Extract Per Servings, 120 Capsules for 40 Servings Per Bottle - Vegan, GMO Free and Gluten Free;
Andre navn:
|
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Alcoho-associated Cirrhosis (AC) patients
Adults ≥18; A history of alcohol consumption averaging at least 80 grams per day in men or 50 grams per day for women for at least 10 years; 3 capsules of the PDS (pomegranate dietary supplement - Nutricost Pomegranate Extract) - dose of 400 mg
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Nutricost Pomegranate Extract 15,000mg Equivalent from 1,000mg of 15:1 Extract Per Servings, 120 Capsules for 40 Servings Per Bottle - Vegan, GMO Free and Gluten Free;
Andre navn:
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Early-Stage Alcohol-Associated Liver Disease
Adults ≥18; AUD qualifying criteria, plus ALT>40.
3 capsules of the PDS (pomegranate dietary supplement - Nutricost Pomegranate Extract) - dose of 400 mg
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Nutricost Pomegranate Extract 15,000mg Equivalent from 1,000mg of 15:1 Extract Per Servings, 120 Capsules for 40 Servings Per Bottle - Vegan, GMO Free and Gluten Free;
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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To characterize the metabolite and cytokine profiles to inform future trials designed for enhancing cut barrier function
Tidsramme: 2036 yr.
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To evaluate the impact of pomegranate dietary supplements (PDS) on gut microbiome composition and epithelial barrier function in healthy, alcohol use disorder (AUD), early-stage ALD (eALD), and alcohol-associated liver cirrhosis (AC) subjects by characterizing the metabolite and cytokine profiles to inform future trials designed for enhancing cut barrier function in alcohol-associated liver disease (ALD).
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2036 yr.
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If inter-individual variation in gut microbiome is responsible for the production of beneficial metabolites
Tidsramme: 2036 yr.
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To determine if inter-individual variation in gut microbiome is responsible for the production of beneficial metabolites in healthy, AUD, eALD, and AC patients by correlating urolithin levels to inflammatory mediators in both healthy and diseased conditions.
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2036 yr.
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To determine if more correlative studies between produced metabolites, inflammatory mediators, and disease conditions could provide informed decisions during disease progression.
Tidsramme: 2036 yr.
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Develop identifiers for the pathology and treatment development of the study cohorts.
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2036 yr.
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To evaluate the omics of the subject and the microbiomes in their saliva, urine, and stool.
Tidsramme: 2036 yr.
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To evaluate the omics of the subject and the microbiomes in their saliva, urine, and stool.
This will help determine what response changes are genetic changes (both bacterial and human) in saliva; and omics, and genetic changes in stool and urine (both human and bacterial) could illustrate their role in profiling these potential modifiable risk factors for AUD/ALD.
The data could be correlated with the blood sample-derived cytokine, gut dysfunction, and candidate biomarkers of liver (K18s) and AUD severity (neurotransmitters, such as dopamine, GABA, serotonin, etc.)
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2036 yr.
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Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Etterforskere
- Studiestol: Craig J McClain, MD, University of Louisville
- Studieleder: Vatsalya Vatsalya, MD, University of Louisville
- Hovedetterforsker: Venkatakrishna R Jala, PhD, University of Louisville
Publikasjoner og nyttige lenker
Studierekorddatoer
Studer hoveddatoer
Studiestart (Antatt)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Psykiske lidelser
- Patologiske prosesser
- Sykdommer i fordøyelsessystemet
- Leversykdommer
- Stoffrelaterte lidelser
- Kjemisk-induserte lidelser
- Alkoholrelaterte lidelser
- Fibrose
- Levercirrhose
- Leversykdommer, alkoholholdig
- Alkohol-induserte lidelser
- Patologiske tilstander, tegn og symptomer
- Alkoholisme
- Levercirrhose, alkoholholdig
Andre studie-ID-numre
- 21.0999
- 2P50AA024337 (U.S. NIH-stipend/kontrakt)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
IPD-delingstidsramme
Tilgangskriterier for IPD-deling
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
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