Walnuts for Colon Health

Recruiting at 1 trial location

Overseen By Amy Pallotti

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: UConn Health

Must not be taking: Immunosuppressants, Steroids, Antibiotics, Anticoagulants

Disqualifiers: Cancer, Lynch syndrome, Crohn's, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial studies if eating walnuts daily can improve gut bacteria, reduce inflammation, and benefit colon tissue in people having a colonoscopy. Walnuts have been shown in animal studies to inhibit colorectal cancer growth and alter gut microbiota.

Do I have to stop taking my current medications for the trial?

The trial requires participants to stop taking dietary supplements, including probiotics. It also excludes those who have used antibiotics or immunosuppressive agents recently. Other medications are not specifically mentioned, so it's best to discuss with the study team.

What evidence supports the effectiveness of walnuts as a treatment for colon health?

Research suggests that walnuts may help protect against colon inflammation and cancer due to their anti-inflammatory and antioxidant properties. Studies in mice have shown that walnuts can reduce intestinal injury and improve gut health by promoting beneficial bacteria and reducing harmful ones. ^{1 2 3 4 5}

Is it safe for humans to consume walnuts for colon health?

Walnuts are generally safe for most people, but some individuals may have allergies to them. In studies, walnuts have shown benefits for heart health and may help with inflammation, but if you have a nut allergy, you should avoid them. ^{1 2 6 7 8}

How do walnuts differ from other treatments for colon health?

Walnuts are unique for colon health because they contain natural compounds like polyunsaturated fatty acids and antioxidant polyphenols, which may reduce inflammation and support beneficial gut bacteria, potentially lowering the risk of colon cancer. Unlike traditional treatments, walnuts work through dietary intake and have prebiotic effects that promote a healthy gut microbiome. ^{1 2 4 7 9}

Research Team

Christian Jobin, Ph.D.

Principal Investigator

University of Florida

Daniel W. Rosenberg, Ph.D.

Principal Investigator

UConn Health

Eligibility Criteria

This trial is for men and women aged 40-75 who are due for a colonoscopy, have a family history of colorectal cancer (CRC), or had positive fecal tests/colon polyps. Participants must not take dietary supplements/probiotics, avoid certain foods, and be willing to eat walnuts daily. Exclusions include walnut allergy, recent cancer other than skin cancer, severe illnesses, immune disorders, antibiotic use within the last month, and blood coagulation issues.

Inclusion Criteria

I am between 45 and 75 years old and have a history of colon polyps.

Willing and able to provide written informed consent for study participation

I am willing to provide blood, urine, and stool samples as required.

Exclusion Criteria

I have HIV or chronic viral hepatitis.

I haven't taken antibiotics in the last month and won't during the study.

I meet the criteria for Lynch Syndrome or have a history of FAP.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Wash-out

Participants undergo a 7-day wash-out period avoiding foods high in ellagitannins

1 week

1 visit (in-person)

Dietary Intervention

Participants consume 2 ounces of walnuts daily for 21 days while avoiding ellagitannins

3 weeks

2 visits (in-person)

Follow-up

Participants are monitored for changes in microbiome and inflammatory markers, and undergo a colonoscopy

1 week

1 visit (in-person)

Treatment Details

Interventions

• Walnuts (N/A)

Trial Overview The study investigates if eating walnuts affects gut bacteria populations and reduces inflammation in the colon lining. Participants will consume two ounces of walnuts every day for three weeks while avoiding specific foods that could influence the results.

Participant Groups

Group I: Walnut Consumption Experimental Treatment 1 Intervention

Following enrollment, participants will start a 7-day wash-out period where they will be asked to avoid foods and beverages high in ellagitannins. These include pomegranates, hazelnuts, pistachios, walnuts (besides the samples given by the researchers), strawberries, raspberries, blackberries, oak-aged wines and spirits; a full list of foods and beverages to avoid will be provided. Then, participants will consume 2 ounces of walnuts daily with their usual diet while continuing to avoid ellagitannins for 21 days prior to their routine colonoscopy.

Who Is Running the Clinical Trial?

UConn Health

Lead Sponsor

Trials

218

Recruited

59,100+

The Jackson Laboratory for Genomic Medicine

Collaborator

Trials

1

Recruited

200+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

California Walnut Commission

Collaborator

Trials

25

Recruited

36,700+

Spanish National Research Council

Collaborator

Trials

10

Recruited

550+

University of Florida

Collaborator

Trials

1,428

Recruited

987,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

University of Connecticut

Collaborator

Trials

194

Recruited

162,000+

Findings from Research

Walnut phenolic extract (WPE) significantly reduces inflammation in both acute and chronic colitis models in mice, indicating its potential as a treatment for inflammatory bowel disease.

WPE not only inhibits key inflammatory markers and signaling pathways but also reduces tumor development in a model of colitis-associated colon cancer, suggesting its efficacy in preventing cancer related to intestinal inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Walnut phenolic extract inhibits nuclear factor kappaB signaling in intestinal epithelial cells, and ameliorates experimental colitis and colitis-associated colon cancer in mice. Koh, SJ., Choi, YI., Kim, Y., et al.[2020]

Walnut oil (WO) has protective effects against acute intestinal injury in mice, as shown by reduced levels of inflammatory markers like TNF-α, IL-6, and IL-1β after treatment with WO following lipopolysaccharide (LPS) exposure.

The protective mechanism of walnut oil involves the inhibition of the TLR4/NF-κB signaling pathway, leading to decreased apoptosis in jejunum cells and improved antioxidant levels, indicating its potential as a therapeutic dietary supplement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The protective effect of walnut oil on lipopolysaccharide-induced acute intestinal injury in mice. Miao, F., Shan, C., Shah, SAH., et al.[2021]

Dietary supplementation with walnuts significantly reduced colonic mucosal injury in mice after exposure to the ulcerogenic agent dextran sodium sulfate (DSS), with the most notable effect observed at a 14% walnut diet, showing a reduction in ulceration from 7.5% to 0.3%.

Metabolite profiling revealed that walnut supplementation increased levels of beneficial compounds like polyunsaturated fatty acids (PUFAs) and S-adenosylhomocysteine (SAH), which may play a role in protecting against inflammation and promoting recovery from colonic injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary Walnut Supplementation Alters Mucosal Metabolite Profiles During DSS-Induced Colonic Ulceration. Nakanishi, M., Matz, A., Klemashevich, C., et al.[2020]

Walnuts are rich in beneficial compounds like polyunsaturated fatty acids, tocopherols, and ellagitannins, which may help reduce cancer risk and promote a healthy gut microbiome.

The ellagitannins in walnuts are converted by gut bacteria into bioactive compounds called urolithins, which have strong anti-inflammatory properties, supporting the idea that walnuts can be a valuable part of a cancer-preventive diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antioxidant and Anti-Inflammatory Properties of Walnut Constituents: Focus on Personalized Cancer Prevention and the Microbiome. Fan, N., Fusco, JL., Rosenberg, DW.[2023]

Walnut oil (WO) significantly improved gut health in mice by increasing the villous height/crypt depth ratio and enhancing antioxidant enzyme activities, indicating its potential to reduce oxidative stress and inflammation.

The study found that WO shifted gut microbiota from harmful bacteria like Helicobacter to beneficial ones like Lactobacillus, while also boosting immune responses, suggesting its role in preventing gastrointestinal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of walnut (Juglans sigillata) oil on intestinal antioxidant, anti-inflammatory, immunity, and gut microbiota modulation in mice. Miao, F., Shan, C., Shah, SAH., et al.[2021]

The study identified Jug r 4 as a relevant minor allergen in walnut allergy, recognized by 27% of walnut allergic adults, indicating its importance in diagnosing walnut allergy.

Jug r 4 showed a high positive predictive value of 90% for walnut allergy, suggesting that testing for this allergen could improve diagnostic accuracy, especially in patients with co-sensitization to other allergens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A subset of walnut allergic adults is sensitized to walnut 11S globulin Jug r 4. Blankestijn, MA., den Hartog Jager, CF., Blom, WM., et al.[2019]

In a study involving 40 healthy participants aged 50 and older, consuming 43g of walnuts daily for 8 weeks significantly reduced non-HDL cholesterol and apolipoprotein-B levels, which are important markers related to heart disease risk.

Despite these positive changes in cholesterol levels, other factors such as fasting glucose, insulin, and markers of inflammation and endothelial function did not show significant changes, indicating that walnuts may specifically target lipid profiles without affecting other metabolic parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Walnut-enriched diet reduces fasting non-HDL-cholesterol and apolipoprotein B in healthy Caucasian subjects: a randomized controlled cross-over clinical trial. Wu, L., Piotrowski, K., Rau, T., et al.[2022]

In a study involving 45 individuals at risk for cardiovascular disease, a walnut diet led to a significant reduction in central diastolic blood pressure compared to a diet where walnut-derived ALA was replaced with oleic acid, suggesting that whole walnuts may provide unique cardiovascular benefits beyond just their fatty acid content.

All diets tested, including the walnut diet, resulted in lowered total cholesterol and LDL cholesterol levels, indicating that moderate-fat, high-unsaturated-fat diets can improve overall cardiovascular risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Replacing Saturated Fat With Walnuts or Vegetable Oils Improves Central Blood Pressure and Serum Lipids in Adults at Risk for Cardiovascular Disease: A Randomized Controlled-Feeding Trial. Tindall, AM., Petersen, KS., Skulas-Ray, AC., et al.[2021]

The study evaluated 12 different walnut cultivars, revealing that total oil content ranged from 62.6% to 70.3%, indicating a high fat content beneficial for heart health.

All cultivars exhibited a similar amino acid profile, suggesting they provide high-quality protein, which is important for overall nutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemical composition of walnuts (Juglans regia L.) grown in New Zealand. Savage, GP.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Walnut phenolic extract inhibits nuclear factor kappaB signaling in intestinal epithelial cells, and ameliorates experimental colitis and colitis-associated colon cancer in mice. [2020]

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

The protective effect of walnut oil on lipopolysaccharide-induced acute intestinal injury in mice. [2021]

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

Dietary Walnut Supplementation Alters Mucosal Metabolite Profiles During DSS-Induced Colonic Ulceration. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Antioxidant and Anti-Inflammatory Properties of Walnut Constituents: Focus on Personalized Cancer Prevention and the Microbiome. [2023]

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

Effect of walnut (Juglans sigillata) oil on intestinal antioxidant, anti-inflammatory, immunity, and gut microbiota modulation in mice. [2021]

6. England pubmed.ncbi.nlm.nih.gov

A subset of walnut allergic adults is sensitized to walnut 11S globulin Jug r 4. [2019]

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

Walnut-enriched diet reduces fasting non-HDL-cholesterol and apolipoprotein B in healthy Caucasian subjects: a randomized controlled cross-over clinical trial. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Replacing Saturated Fat With Walnuts or Vegetable Oils Improves Central Blood Pressure and Serum Lipids in Adults at Risk for Cardiovascular Disease: A Randomized Controlled-Feeding Trial. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Chemical composition of walnuts (Juglans regia L.) grown in New Zealand. [2019]