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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how gut bacteria process compounds called polyphenols, found in apples, and how this might affect health benefits. Participants will follow a special 3-day diet, either with or without apple polyphenols, to observe how their gut bacteria handle these compounds. The trial suits adults aged 18 to 45 who can adhere to a specific diet and avoid foods like tea and chocolate for a few weeks. Participants must also visit the study site eight times and provide urine and fecal samples. As an unphased study, this trial offers a unique opportunity to contribute to the scientific understanding of dietary impacts on gut health.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that apple polyphenols are generally safe for people. One study tested a polyphenol extract from unripe apples, called Applephenon, and found it safe with no harmful effects. Another study with healthy adults demonstrated that taking apple polyphenols did not negatively affect their immune cells or gut bacteria. These findings suggest that apple polyphenols are well-tolerated and safe to consume. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using apple polyphenols for gut health because they offer a natural alternative to traditional treatments that often rely on probiotics or medications. Unlike probiotics, which introduce live bacteria into the gut, apple polyphenols work by enhancing the gut's existing microbial environment. This approach could lead to improved digestion and gut health without the need for live bacterial cultures. Additionally, apple polyphenols are derived from apples, making them an easily accessible and potentially safer option for those seeking dietary improvements.

What evidence suggests that apple polyphenols could be effective for gut health?

Research has shown that natural compounds in apples, known as apple polyphenols, can benefit gut health. These compounds reduce swelling in the colon and improve the balance of gut bacteria. In this trial, participants will be assigned to different treatment arms, including one with apple catechin, to evaluate its effects on gut health. One study found that people who consumed apple polyphenols experienced better digestion and more regular bowel movements than those who did not. Another study suggested that regularly consuming apple polyphenols can protect against long-term gut problems. These findings indicate that apple polyphenols might effectively support gut health and improve digestion. ^{3 4 5 6 7}

Who Is on the Research Team?

Margaret Slavin, PhD

Principal Investigator

University of Maryland, College Park

Are You a Good Fit for This Trial?

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

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

Known allergic reactions to components of the foods or beverages of the study diet (soy, wheat, dairy, peanut, tree nuts, apples, eggs) or any history of anaphylactic food allergy

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10856038/

Phenolic Compounds from Apples: From Natural Fruits to ...

The apple polyphenols alleviated mucosal damage in the colon, inhibited the inflammation in the colon, regulated the gut microbiota, and strengthened the ...

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0924224424000955

Exploring the potential of apple (poly)phenols: A systematic ...

The reviewed literature suggests a protective role of apple (poly)phenols, at an intake of approximately 800 mg/day for 4 weeks or more, against chronic ...

3.

pubs.acs.org

pubs.acs.org/doi/10.1021/acs.jafc.5c05176

Beneficial Effects of Apple Polyphenol Extract and Time ...

Time-restricted feeding (TRF) and apple polyphenol extract (APE) emerged as promising adjuvant strategies for managing inflammation and gut ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4488768/

Apples and Cardiovascular Health—Is the Gut Microbiota a ...

Moreover, up to 90% of dietary plant polyphenols [94] including apples, reach the colon intact [48,59,95,96].

5.

tandfonline.com

tandfonline.com/doi/full/10.1080/19390211.2025.2539878

Apple Polyphenols and Defecation in Overweight Adults ...

After the 12-week intervention, the Apple polyphenol group had a significantly higher weekly defecation frequency versus the Placebo group (7.0 ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8065949/

A Polyphenol Enriched Variety of Apple Alters Circulating ...

A polyphenol enriched variety of apple alters circulating immune cell gene expression and faecal microbiota composition in healthy adults.

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/15110105/

The toxicology and safety of apple polyphenol extract

Here, we tested the consumption safety of Applephenon, which is a polyphenol extract produced from unripe apples. The Ames test without S9 mixture revealed ...