Cardiometabolic Benefits of Potatoes Mediated Along the Gut-Vessel Axis in Adults With Metabolic Syndrome

Study Overview
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Brief Summary
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This study is focused on assessing potential health benefits of daily consumption of potatoes, specifically its resistant starch content (i.e. nondigestible carbohydrate), on blood vessel and gut health function in adults with metabolic syndrome. It is expected that the daily consumption of potatoes for two weeks, within a diet that follows the Dietary Guidelines for Americans, will improve blood vessel function in association with decreasing gut permeability (leaky gut) that results in the absorption of bacterial toxins that reside in the intestine. Outcomes will therefore support dietary recommendations for potatoes to support vascular and gastrointestinal health.

Detailed Description
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Cardiovascular disease is a major public health concern in the United States, where it accounts for 1 in 4 deaths every year. Vascular endothelial dysfunction is an early event leading to cardiovascular disease and can be caused by postprandial hyperglycemia. Cardiovascular disease is also characterized by metabolic endotoxemia. Metabolic endotoxemia describes increased circulating levels of gut-derived endotoxin (lipopolysaccharide; a bacterial product derived from Gram-negative bacteria in the intestines) that results from gut barrier dysfunction, a phenomenon that is common in metabolic syndrome. Studies in animals and humans have shown that consumption of resistant starch (a type of carbohydrate found in potatoes among other foods) can help to improve vascular and gut health. This clinical trial will therefore investigate the extent to which potatoes can improve microbiota composition, alleviate metabolic endotoxemia, and improve vascular function. It is hypothesized that 2-week daily ingestion of potatoes within a diet that meets the Dietary Guidelines for Americans will limit metabolic endotoxemia by decreasing gut barrier permeability and alleviating gut dysbiosis while separately improving vascular function by limiting postprandial hyperglycemia. This study will address the following objectives: 1) define changes in gut barrier function in association with improved gut microbiota composition, increased fecal short chain fatty acid (SCFA) production, and decreased serum endotoxin, 2) define changes in postprandial glycemic responses and endotoxemia, and 3) define changes in gut hormones that promote glycemic control and changes in markers of oxidative stress in relation to improvements in endothelial vascular function, all following 2-week potato consumption. To test the hypothesis, all participants will complete a randomized cross-over trial where they will receive a potato or bagel along with a diet that meets the Dietary Guidelines for Americans for 2 weeks. They will then undergo a 2-h postprandial study to define the influence of potato consumption on vascular function, glycemic control, and endotoxin translocation. Upon completing the intervention, participants will undergo a gut permeability test, fecal samples will be collected for microbiota composition analysis, and blood samples will be collected to assess endotoxin and inflammatory markers. Upon successfully completing this study, it is anticipated that chronic consumption of potatoes will be demonstrated to be an effective dietary strategy to reduce metabolic endotoxemia, improve gut health, and improve vascular function.

Official Title
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Cardiometabolic Benefits of Potatoes Mediated Along the Gut-Vessel Axis in Adults With Metabolic Syndrome

Conditions
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Cardiovascular Diseases, Endotoxemia, Endothelial Dysfunction, Postprandial Hyperglycemia, Gut Health

Intervention / Treatment
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* Other: Bagel
* Other: Potato


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fasting glucose 100-125 mg/dL Waist circumference >102 cm (men), >88 cm (women) Fasting triglyceride >150 mg/dL Fasting HDL cholesterol <40 mg/dL (men), <50 mg/dL (women) Non-smoker Non-dietary supplement user (>1-mo) Free of gastrointestinal disorders, cardiovascular disease, cancer No recent use of antibiotics or any medications affecting glycemia, lipidemia, or blood pressure Exclusion Criteria: Use of anti-inflammatory agents or probiotics Vegetarian, gluten-intolerant, carbohydrate-restricted diet Alcohol intake >2 drinks/d >7 hours/week of aerobic activity Women who are pregnant or lactating or have initiated or changed birth control in the past 3-months Taking medications that affect blood sugar, blood pressure, blood vessel health, or inflammation High blood pressure or any vascular diseases HIV, hepatitis, or blood disorders such as hemophilia Gastrointestinal disorders Cancer (current or past history) Anemia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Bagel diet<br>Bagel consumed daily for 2 weeks | Other: Bagel<br>* A bagel will be consumed daily for 2 weeks.<br>|
| Experimental: Potato diet<br>Potato consumed daily for 2 weeks | Other: Potato<br>* A potato will be consumed daily for 2 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endotoxin | Fasting serum endotoxin concentration | Day 14 | 
| Vascular endothelial function | Area under curve (change from baseline) for flow-mediated dilation of brachial artery | Day 14 Postprandial (0, 30, 60, 90, 120 minutes) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Glucose Day 0 | Fasting plasma glucose | Fasting glucose on Day 0 | 
| Fasting Glucose Day 14 | Fasting plasma glucose | Fasting glucose on Day 14 | 
| Fasting Insulin Day 0 | Fasting plasma insulin | Fasting insulin on Day 0 | 
| Fasting Insulin Day 14 | Fasting plasma insulin | Fasting insulin on Day 14 | 
| Postprandial Insulin | Plasma insulin concentration area under curve change from baseline | Day 14 postprandial (0, 30, 60, 90, 120 minutes) | 
| Postprandial Glucose | Postprandial plasma glucose concentration area under curve change from baseline | Day 14 postprandial (0, 30, 60, 90, 120 minutes) | 
| Fasting Endotoxin | Fasting serum endotoxin concentration | Day 0 | 
| Postprandial Endotoxin | Postprandial serum endotoxin concentration area under curve change from baseline | Day 14 postprandial (0, 30, 60, 90, 120 minutes) | 
| Lactulose/mannitol ratio | Urinary concentration of the non-digestible sugars lactulose/mannitol | Day 14, 0-5 hours post-consumption of sugar probes | 
| Sucralose/erythritol ratio | Urinary concentration of the non-digestible sugars sucralose/erythritol | Day 14, 6-24 hours post-consumption of sugar probes | 
| Fecal butyrate | Fecal concentration of butyrate | Day 14 | 
| Fecal acetate | Fecal concentration of acetate | Day 14 | 
| Fecal propionate | Fecal concentration of propionate | Day 14 | 
| Postprandial Cholecystokinin | Plasma CCK area under curve change from baseline | Day 14 postprandial (0, 30, 60, 90, 120 minutes) | 
| Postprandial glucagon-like peptide-1 | Plasma GLP-1 area under curve change from baseline | Day 14 postprandial (0, 30, 60, 90, 120 minutes) | 
| Postprandial Gastric inhibitory peptide | Plasma GIP area under curve change from baseline | Day 14 postprandial (0, 30, 60, 90, 120 minutes) | 
| Fasting cholecystokinin | Fasting plasma concentration of CCK | Day 14 | 
| Fasting GLP-1 | Fasting plasma concentration of GLP-1 | Day 14 | 
| Fasting Gastric inhibitory peptide | Fasting plasma concentration of GIP | Day 14 | 
| Postprandial NOx | Plasma total nitrite/nitrate area under curve change from baseline | Day 14 postprandial (0, 30, 60, 90, 120 minutes) | 
| Fasting NOx | Fasting plasma concentration of nitrite/nitrate | Day 14 | 
| Postprandial Malondialdehyde (MDA) | Plasma MDA concentration, biomarker of oxidative stress area under curve change from baseline | Day 14 postprandial (0, 30, 60, 90, 120 minutes) | 
| Fasting Malondialdehyde (MDA) | Fasting plasma MDA concentration, biomarker of oxidative stress | Day 14 | 
| Fasting Vascular Endothelial Function | Fasting flow-mediated dilation of the brachial artery | Day 14 | 
| Vitamin C | Fasting vitamin C concentration, biomarker of oxidative stress | Day 14 | 
| cIMT | Carotid intima-media thickness | Day 14 | 
| Day 0 weight | Weight in kilograms | Day 0 | 
| Day 7 weight | Weight in kilograms | Day 7 | 
| Day 14 weight | Weight in kilograms | Day 14 | 
| Day 0 height | Height in centimeters | Day 0 | 
| Day 7 height | Height in centimeters | Day 7 | 
| Day 14 height | Height in centimeters | Day 14 | 
| Day 0 waist circumference | Waist circumference in centimeters | Day 0 | 
| Day 7 waist circumference | Waist circumference in centimeters | Day 7 | 
| Day 14 waist circumference | Waist circumference in centimeters | Day 14 | 
| Day 0 diastolic blood pressure | Diastolic blood pressure | Day 0 | 
| Day 7 diastolic blood pressure | Diastolic blood pressure | Day 7 | 
| Day 14 diastolic blood pressure | Diastolic blood pressure | Day 14 | 
| Day 0 systolic blood pressure | Systolic blood pressure | Day 0 | 
| Day 7 systolic blood pressure | Systolic blood pressure | Day 7 | 
| Day 14 systolic blood pressure | Systolic blood pressure | Day 14 |