Elucidating the Effect of Dietary Stearic Acid on the Regional Heterogeneity of the Gut Microbiome and Metabolome: Focus on Bile Acid Metabolism (SAMPill Study)

NCT07766915 | Not Yet Recruiting

• 2 other identifiers: 7098GRANT14224177
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Stearic acid and palmitic acid are two common consumed saturated fatty acids found in foods. Palmitic acid is associated with increases in blood cholesterol, whereas stearic acid is generally considered neutral with respect to blood cholesterol. However, the mechanisms underlying these different effects are not fully understood. The goal of this clinical trial is to determine how replacing dietary palmitic acid with stearic acid affects microorganisms living in the gastrointestinal tract (gut microbiome) and the metabolites they produce, including secondary bile acids, and whether these changes influence heart and metabolic health in postmenopausal women. The main question it aims to answer is whether the cholesterol lowering effect of dietary stearic acid, compared to dietary palmitic acid is due to changes in the composition and function of the gut microbiome and bile acid metabolism. Participants will consume a controlled diet high in palmitic acid for a 10-day run-in period, followed by a controlled diet high in stearic acid for 28 days. During the study, participants will provide biological samples, including blood samples collected in both fasting and non-fasting states, for assessment of cardiometabolic outcomes. Participants will also swallow mini-pills designed to collect samples from different regions of the gastrointestinal tract to assess the gut microbiome and related metabolites. Results will contribute to understanding the relationship between stearic acid mediated microbiota effects on cardiometabolic heath.

Conditions

CVD Risk

Keywords

stearic acid; bile acid metabolism; post-menopausal women; dietary intervention; saturated fatty acids; gut microbiome

Outcome Measures

Primary Outcomes (5)

• Relative Abundance of Gut Microbial Taxa (%)

  Gut microbial composition in gastrointestinal luminal and stool samples will be assessed using whole-genome shotgun metagenomic sequencing and reported as relative abundance (%). Alpha and beta diversity will also be evaluated as part of the microbiome analyses.

  End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.

• Relative Abundance of Gut Microbial Functional Pathways (%)

  Gut microbial functional pathways in gastrointestinal luminal and stool samples will be assessed from whole-genome shotgun metagenomic sequencing data using bioinformatic pathway analysis and reported as relative abundance (%). Analyses will include pathways related to bile acid metabolism as well as other microbial metabolic pathways.

  End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.

• Concentrations of Bile Acids in Gastrointestinal Luminal Samples (nmol/mL)

  Primary and secondary bile acids, including conjugated and unconjugated bile acids, will be quantified in gastrointestinal luminal samples using targeted mass spectrometry and reported as nmol/mL.

  End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.

• Concentrations of Bile Acids in Plasma (nmol/mL)

  Primary and secondary bile acids, including conjugated and unconjugated bile acids, will be quantified in fasting and postprandial plasma using targeted mass spectrometry and reported as nmol/mL.

  End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.

• Concentrations of Bile Acids in Stool (nmol/mg dry weight)

  Primary and secondary bile acids, including conjugated and unconjugated bile acids, will be quantified in stool using targeted mass spectrometry, normalized to fecal dry weight, and reported as nmol/mg dry weight.

  End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.

Secondary Outcomes (3)

• Plasma Metabolite Concentrations (µmol/L)

  End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.

• Fecal Metabolite Concentrations (nmol/mg dry weight)

  End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.

• Serum Cholesterol metabolism markers

  End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.

Other Outcomes (6)

• Fibroblast growth factor 19 (FGF19) Concentration (ng/mL)

  End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.

• Plasma Lipid Concentrations (mg/dL)

  End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.

• Serum Glucose Concentration (mg/dL)

  End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.

Study Arms (1)

Palmitic Acid Run-In Followed by Stearic Acid Diet

EXPERIMENTAL

A controlled 38-day intervention with a10 day run-in phase with a diet high in palmitic acid to stabilize baseline variables, followed by a 28 diet phase with a diet high in stearic acid

Other: High Palmitic Acid Diet; Other: High Stearic Acid Diet

Interventions

High Palmitic Acid Diet OTHER

The main source of palmitic acid that will be used to prepare the meals will include blends of palm oil and safflower oil, which are commercially available. These blends will be incorporated into foods such as muffins, cookies, sauces, and mixed dishes (e.g., casseroles).

Palmitic Acid Run-In Followed by Stearic Acid Diet

High Stearic Acid Diet OTHER

The main source of stearic acid that will be used to prepare the meals will include blends of cocoa butter, fully hydrogenated soybean and safflower oil, all of which are commercially available. These blends will be incorporated into foods such as muffins, cookies, sauces, and mixed dishes (e.g., casseroles).

Palmitic Acid Run-In Followed by Stearic Acid Diet

Eligibility Criteria

• Age: 50 Years+
• Gender Eligibility Details: Post menopausal females
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal women (defined as complete natural cessation of menses for \>12 months or a bilateral oophorectomy), who are not currently using hormone replacement therapy (HRT) or gender-affirming hormone treatments
• Age \>50 years
• BMI \>20 to \<35 kg/m2, inclusive
• Non-smoker or former smoker who quit \> 6 months
• Normotensive with or without medication
• Normal gastrointestinal function with regular bowel movements at least once every other day
• Willingness to swallow the mini-pills
• Willingness to collect and return multiple stool samples
• Adequate refrigerator and freezer space to store study meals
• Intent to remain in the greater Boston area during the intervention periods

You may not qualify if:

• Allergy/intolerance/religious reasons to avoid study meals or food ingredients
• Regular use of dietary supplements, pre/probiotics, laxatives or fiber supplements (except multivitamins) within the past 3 months
• Use of steroids (excluding topical) within the past 3 months
• Regular use of aspirin (except baby aspirin), NSAIDS, or anti diarrheal medication
• Current smokers or former smokers who quit \< 6 months ago, and use of nicotine replacement products within the last 6 months
• Chronic constipation
• Use of oral antibiotics within the past 3 months.
• Use of dental prophylaxis within the past 3 months
• Regular use of stomach acid lowering and weight loss medications such as GLP-1 agonists
• Planned colonoscopy 3 months prior to or during the study period
• Swallowing disorder or inability or difficulty taking pills
• Malabsorptive and inflammatory bowel disease, diverticulosis, and history of diverticulitis, gastric esophageal/intestinal surgery, including lap banding or bariatric surgery.
• History of bowel obstruction, gallstones, gastroparesis, pancreas and liver/gallbaldder disorders.
• Any form of active substance abuse or dependence (including drug or alcohol abuse).
• Established major chronic diseases such as CVD, diabetes, active cancer within the last 5 years, or any significant medical condition at the study MD's discretion

Sponsors & Collaborators

• Tufts University: lead

Study Sites (1)

Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University

Boston, Massachusetts, 02111, United States

Location

Related Publications (3)

• Rodriguez-Morato J, Galluccio J, Dolnikowski GG, Lichtenstein AH, Matthan NR. Comparison of the Postprandial Metabolic Fate of U-13C Stearic Acid and U-13C Oleic Acid in Postmenopausal Women. Arterioscler Thromb Vasc Biol. 2020 Dec;40(12):2953-2964. doi: 10.1161/ATVBAHA.120.315260. Epub 2020 Oct 1.

  PMID: 32998517 BACKGROUND

• Meng H, Matthan NR, Wu D, Li L, Rodriguez-Morato J, Cohen R, Galluccio JM, Dolnikowski GG, Lichtenstein AH. Comparison of diets enriched in stearic, oleic, and palmitic acids on inflammation, immune response, cardiometabolic risk factors, and fecal bile acid concentrations in mildly hypercholesterolemic postmenopausal women-randomized crossover trial. Am J Clin Nutr. 2019 Aug 1;110(2):305-315. doi: 10.1093/ajcn/nqz095.

  PMID: 31179489 BACKGROUND

• Kris-Etherton PM, Griel AE, Psota TL, Gebauer SK, Zhang J, Etherton TD. Dietary stearic acid and risk of cardiovascular disease: intake, sources, digestion, and absorption. Lipids. 2005 Dec;40(12):1193-200. doi: 10.1007/s11745-005-1485-y.

  PMID: 16477802 BACKGROUND

Central Study Contacts

Nirupa R Matthan, PhD

CONTACT

6175563114; nirupa.matthan@tufts.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientist 1/Associate Professor

Model Details: Pre-post study design. The entire study period will be approximately 38 days, starting with a 10-day controlled run-in phase (high palmitic acid diet) to stabilize baseline variables, and a 28-day controlled feeding phase (high stearic acid diet).

Study Record Dates

• First Submitted: August 4, 2026
• First Posted: August 17, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): August 1, 2029
• Last Updated: August 17, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: Data will be available beginning 6 months after publication of the primary study results and up to 7 years, thereafter.
• Access Criteria: De-identified individual participant data and supporting study documentation will be made available to researchers and the public through established data repositories, as appropriate. Data generated from this study may be deposited in repositories such as the Ag Data Commons, the National Agricultural Library, the Human Metabolome Database (HMDB), and the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA), consistent with repository requirements and applicable regulations. Supporting information, including study protocols, data dictionaries, metadata, and analytic documentation, will be provided as appropriate to facilitate data reuse. Data will be accessible through the respective repository access procedures and policies.

Locations

US (1)