Apple Polyphenol Diet for Gut Health

(GutMMAP Trial)

Overseen By Margaret Slavin, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Maryland, College Park

Must not be taking: Antacids, Antibiotics

Disqualifiers: Pregnancy, Food allergies, Renal, others

Compensation: Varies

Number of Visits: 2

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you regularly use antacids or acid reducers, or if you've used antibiotics in the past month.

What data supports the effectiveness of the treatment Apple Polyphenols for gut health?

Research shows that apple polyphenols can help improve gut health by reducing intestinal infections and inflammation, as seen in studies with mice and rats. They also show potential in reducing oxidative damage and cancer risk in colon cells, suggesting benefits for overall gut health. ^{1 2 3 4 5}

Is apple polyphenol extract safe for human consumption?

Research shows that apple polyphenol extract, used in food and supplements, is generally safe for humans. Tests found no significant harmful effects at typical dietary levels, although high concentrations showed slight mutagenicity (potential to cause genetic changes) in one test. ^{1 4 5 6 7}

How does the apple polyphenol diet treatment differ from other treatments for gut health?

The apple polyphenol diet is unique because it uses natural compounds found in apples to improve gut health by enhancing beneficial gut bacteria and reducing inflammation. Unlike other treatments, it acts as a prebiotic, supporting the growth of good bacteria in the gut, and has shown potential in reducing intestinal infections in studies. ^{1 6 8 9 10}

What is the purpose of this trial?

The goal of this controlled feeding trial is to learn about the metabolism of polyphenols, a common class of compounds found in plant-based foods, by the gut microbiome. It will evaluate how differences in gut bacteria across individuals influence metabolism of polyphenols from foods, which may influence health benefits that people receive from different foods.

Research Team

Margaret Slavin, PhD

Principal Investigator

University of Maryland, College Park

Eligibility Criteria

This trial is for healthy individuals aged 18-45 with a BMI of 18.5-40 who can eat specific foods and avoid high catechin items like tea and chocolate for four weeks. Participants must be willing to provide urine and fecal samples, attend eight study visits, and adhere to the diet plan. Those with allergies to study foods, recent antibiotic use, pregnancy or lactation, or certain medical conditions cannot join.

Inclusion Criteria

You are able to consume the prescribed foods and beverages, and willing to comply with the dietary plan.

You are willing to provide biological samples as outlined in the study.

You agree to abstain from consuming high catechin foods (tea, chocolate) for a period of four weeks.

Exclusion Criteria

Has a pacemaker, implanted defibrillator, or other implanted electronic device

I regularly use antacids or acid reducers.

Pregnancy or lactation, within 3 months post-partum (regardless of breastfeeding) at screening or planning to become pregnant during the study duration

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diet Phase 1

Participants consume an apple catechin diet for 3 days

3 days

1 visit (in-person)

Washout

A washout period between diet phases to clear previous diet effects

10 days

Diet Phase 2

Participants consume a low catechin diet for 3 days

3 days

1 visit (in-person)

Follow-up

Participants are monitored for differences in microbiome profiles and catechin metabolites

1-2 weeks

Treatment Details

Interventions

• Apple Polyphenols

Trial Overview The trial is testing how gut bacteria metabolize apple polyphenols by comparing two diets: one rich in apple catechins (natural compounds found in apples) versus a low-catechin diet. It aims to understand individual differences in processing these compounds which could affect health benefits from food.

Participant Groups

Group I: Apple catechin Experimental Treatment 1 Intervention

A 3-day controlled diet

Group II: Low catechin Placebo Group 1 Intervention

A 3-day controlled diet

Who Is Running the Clinical Trial?

University of Maryland, College Park

Lead Sponsor

Trials

163

Recruited

46,800+

University of Hawaii Cancer Research Center

Collaborator

Trials

11

Recruited

2,100+

MaineHealth

Collaborator

Trials

76

Recruited

43,800+

Findings from Research

Mice treated with apple polyphenols showed higher survival rates and reduced diarrhea symptoms in a model of Clostridioides difficile infection, indicating their potential efficacy in combating intestinal infections.

Apple polyphenols improved intestinal health by enhancing anti-inflammatory effects, maintaining colon barrier integrity, and promoting beneficial gut microbiota, suggesting they could serve as a prebiotic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apple Polyphenol Extract Suppresses Clostridioides difficile Infection in a Mouse Model. Wu, Z., Xu, Q., Li, A., et al.[2022]

Apple juice extracts, particularly from cider apples, significantly reduce oxidative DNA damage in human colon cell lines, indicating their potential protective effects against intestinal oxidative stress.

The effectiveness of these extracts is influenced by their polyphenolic content, with compounds like quercetin and phloretin showing the highest antioxidant capacity, suggesting that specific apple varieties and extraction methods can enhance their health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polyphenolic apple juice extracts and their major constituents reduce oxidative damage in human colon cell lines. Schaefer, S., Baum, M., Eisenbrand, G., et al.[2015]

In a study with 27 male mice, supplementation with polyphenol-rich apple extracts significantly reduced the number of neoplastic lesions, such as polyps, in mice induced with colorectal cancer, suggesting a protective effect against cancer progression.

While the apple extract did not affect body weight or energy metabolism, it helped preserve adipose tissue mass and reduced signs of cachexia, indicating potential benefits for overall health in the context of obesity-related cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azoxymethane-Induced Colorectal Cancer Mice Treated with a Polyphenol-Rich Apple Extract Show Less Neoplastic Lesions and Signs of Cachexia. Marzo, F., Milagro, FI., Barrenetxe, J., et al.[2021]

A polyphenol extract from apples significantly reduced the severity of colitis in rats, restoring key inflammatory biomarkers to baseline levels after 14 days of treatment.

The therapeutic effects of apple polyphenols are linked to their ability to modulate COX-2 and TNF-α levels, and they may help protect tissue transglutaminase from degradation by calpain, suggesting a potential new approach for treating ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apple polyphenols extract (APE) improves colon damage in a rat model of colitis. D'Argenio, G., Mazzone, G., Tuccillo, C., et al.[2022]

Apple polyphenols have been shown to significantly reduce the survival of colon adenoma (LT97) and carcinoma (HT29) cell lines, with the most potent effect observed from the AE03 extract, which had a higher concentration of quercetin compounds.

Fermentation of apple extracts decreased their bioactivity by approximately three-fold, indicating that while fermentation increases short-chain fatty acids, it also reduces the chemoprotective properties of the polyphenols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apple polyphenols and products formed in the gut differently inhibit survival of human cell lines derived from colon adenoma (LT97) and carcinoma (HT29). Veeriah, S., Hofmann, T., Glei, M., et al.[2011]

Three apple varieties (Renetta Canada, Golden Delicious, and Pink Lady) significantly altered gut microbiota composition and increased beneficial short-chain fatty acids (SCFAs) in vitro, indicating potential health benefits.

Renetta Canada specifically enhanced the abundance of beneficial bacteria like Faecalibacterium prausnitzii and increased levels of polyphenol microbial metabolites, suggesting it may have a particularly strong positive impact on gut health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Commercial Apple Varieties on Human Gut Microbiota Composition and Metabolic Output Using an In Vitro Colonic Model. Koutsos, A., Lima, M., Conterno, L., et al.[2018]

Applephenon, a polyphenol extract from unripe apples, showed slight mutagenicity in the Ames test at very high concentrations, but no significant mutagenicity was found in other tests, indicating it is generally safe.

In both acute and 90-day subchronic toxicity tests at a dose of 2000 mg/kg, Applephenon did not show any harmful effects on health, confirming its safety for average dietary consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The toxicology and safety of apple polyphenol extract. Shoji, T., Akazome, Y., Kanda, T., et al.[2011]

Traditional apple varieties have higher total phenolic contents compared to commercial varieties, which may enhance their health benefits during digestion, as both types show similar bioaccessibility of phenolics (40-80% for flesh and 39-65% for peel).

The study found no significant evidence that phenolic compounds in apples reduce allergenicity, suggesting that while they may offer health benefits, they do not impact the allergenic potential of apple varieties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analyzing Bioaccessibility of Polyphenols in Six Commercial and Six Traditional Apples (Malus domestica Borkh.) during In Vitro and Ex Vivo Oral Digestion. Kaeswurm, JAH., Sempio, R., Manca, F., et al.[2023]

Apple products, particularly extracts rich in oligomeric procyanidins, have demonstrated multiple cancer-preventive mechanisms in laboratory studies, including antioxidant and anti-inflammatory effects, as well as the ability to induce apoptosis in cancer cells.

Regular consumption of apples may lower the risk of lung and colon cancer, supported by epidemiological studies, suggesting that eating one or more apples a day could be beneficial for cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer chemopreventive potential of apples, apple juice, and apple components. Gerhauser, C.[2022]

The study found that after consuming 1 L of apple juice, only a small percentage (5.3% in serum and 3.5% in urine) of the original polyphenols were recovered, indicating limited absorption and metabolism of these compounds in humans.

Significant transformations of apple polyphenols occurred during digestion, including the complete degradation of procyanidin B(2) and conversion of quercetin into various metabolites, which highlights the complex metabolic pathways these compounds undergo in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal transit and systemic metabolism of apple polyphenols. Kahle, K., Kempf, M., Schreier, P., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Apple Polyphenol Extract Suppresses Clostridioides difficile Infection in a Mouse Model. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Polyphenolic apple juice extracts and their major constituents reduce oxidative damage in human colon cell lines. [2015]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Azoxymethane-Induced Colorectal Cancer Mice Treated with a Polyphenol-Rich Apple Extract Show Less Neoplastic Lesions and Signs of Cachexia. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Apple polyphenols extract (APE) improves colon damage in a rat model of colitis. [2022]

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

Apple polyphenols and products formed in the gut differently inhibit survival of human cell lines derived from colon adenoma (LT97) and carcinoma (HT29). [2011]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Commercial Apple Varieties on Human Gut Microbiota Composition and Metabolic Output Using an In Vitro Colonic Model. [2018]

7. England pubmed.ncbi.nlm.nih.gov

The toxicology and safety of apple polyphenol extract. [2011]

8. Germany pubmed.ncbi.nlm.nih.gov

Analyzing Bioaccessibility of Polyphenols in Six Commercial and Six Traditional Apples (Malus domestica Borkh.) during In Vitro and Ex Vivo Oral Digestion. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Cancer chemopreventive potential of apples, apple juice, and apple components. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Intestinal transit and systemic metabolism of apple polyphenols. [2021]