Cardiovascular Diseases, Endotoxemia, Endothelial Dysfunction, Postprandial Hyperglycemia, Gut Health
Conditions
Brief summary
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
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.
Interventions
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endotoxin | Day 14 | Fasting serum endotoxin concentration |
| Vascular Endothelial Function | Day 14 Postprandial (0, 30, 60, 90, 120 minutes) | Area under curve (change from baseline) for brachial artery flow-mediated dilation (FMD). The unit for FMD is %, which is calculated as: \[vessel diameter in millimeters (post-occlusion) - vessel diameter in millimeters (pre-occlusion)\] / vessel diameter in millimeters (pre-occlusion) x 100. FMD(%) is then used to caluclate area under the curve based on independent measures of FMD at 0-120 minutes) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Glucose Day 0 | Fasting glucose on Day 0 | Fasting plasma glucose |
| Fasting Glucose Day 14 | Fasting glucose on Day 14 | Fasting plasma glucose Day 14 |
| Fasting Insulin Day 0 | Fasting insulin on Day 0 | Fasting plasma insulin |
| Fasting Insulin Day 14 | Fasting insulin on Day 14 | Fasting plasma insulin Day 14 |
| Postprandial Insulin | Day 14 postprandial (0, 30, 60, 90, 120 minutes) | Plasma insulin concentration area under curve change from baseline |
| Postprandial Glucose | Day 14 postprandial (0, 30, 60, 90, 120 minutes) | Postprandial plasma glucose concentration area under curve change from baseline |
| Fasting Endotoxin | Day 0 | Fasting serum endotoxin concentration |
| Postprandial Endotoxin | Day 14 postprandial (0, 30, 60, 90, 120 minutes) | Postprandial serum endotoxin concentration area under curve change from baseline |
| Lactulose/Mannitol Ratio | Day 14, 0-5 hours post-consumption of sugar probes | Urinary concentration of the non-digestible sugars lactulose/mannitol (mg/mg) |
| Sucralose/Erythritol Ratio | Day 14, 6-24 hours post-consumption of sugar probes | Urinary concentration of the non-digestible sugars sucralose/erythritol |
| Fecal Butyrate | Day 14 | Fecal concentration of butyrate |
| Fecal Acetate | Day 14 | Fecal concentration of acetate |
| Fecal Propionate | Day 14 | Fecal concentration of propionate |
| Postprandial Cholecystokinin | Day 14 postprandial (0, 30, 60, 90, 120 minutes) | Plasma CCK area under curve change from baseline |
| Fasting Cholecystokinin | Day 14 | Fasting plasma concentration of CCK |
| Postprandial NOx | Day 14 postprandial (0, 30, 60, 90, 120 minutes) | Plasma total nitrite/nitrate area under curve change from baseline |
| Fasting NOx | Day 14 | Fasting plasma concentration of nitrite/nitrate |
| Postprandial Malondialdehyde (MDA) | Day 14 postprandial (0, 30, 60, 90, 120 minutes) | Plasma MDA concentration, biomarker of oxidative stress area under curve change from baseline |
| Fasting Malondialdehyde (MDA) | Day 14 | Fasting plasma MDA concentration, biomarker of oxidative stress |
| Fasting Vascular Endothelial Function | Day 14 | Fasting flow-mediated dilation of the brachial artery. Measure is calculated as: \[post-occlusion vessel diameter (mm) - pre-occlusion vessel diameter (mm) / pre-occlusion vessel diameter (mm)\] x 100 |
| Vitamin C | Day 14 | Fasting vitamin C concentration, biomarker of oxidative stress |
| cIMT | Day 14 | Carotid intima-media thickness. Mean thickness of left and right carotid artery intima media. |
| Day 14 BMI | Day 14 | Body mass index calculated as kg weight per meters squared |
| Day 0 Waist Circumference | Day 0 | Waist circumference in centimeters |
| Day 14 Waist Circumference | Day 14 | Waist circumference in centimeters |
| Day 0 Diastolic Blood Pressure | Day 0 | Diastolic blood pressure on Day 0 |
| Day 14 Diastolic Blood Pressure | Day 14 | Diastolic blood pressure on Day 14 |
| Day 0 Systolic Blood Pressure | Day 0 | Systolic blood pressure on Day 0 |
| Day 14 Systolic Blood Pressure | Day 14 | Systolic blood pressure on Day 14 |
| Day 0 BMI | Day 0 | Body mass index calculated as kg weight per meters squared |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Baseline Measures - All Participants Baseline Measures of All Participants Prior To Randomization | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (2 Weeks) | Withdrawal by Subject | 1 | 2 |
| Second Intervention (2 Weeks) | Protocol Violation | 1 | 1 |
Baseline characteristics
| Characteristic | Baseline Measures - All Participants | — |
|---|---|---|
| Age, Continuous | 32.5 years STANDARD_DEVIATION 6.8 | — |
| Body mass index (kg/m^2) | 35 kg/m^2 STANDARD_DEVIATION 5.1 | — |
| Diastolic Blood Pressure (mmHg) | 82.9 mmHg STANDARD_DEVIATION 5.6 | — |
| Plasma Ascorbic Acid (umol/L) | 40.4 umol/L STANDARD_DEVIATION 21.2 | — |
| Plasma Glucose (mg/dl) | 103.7 mg/dL STANDARD_DEVIATION 8.1 | — |
| Plasma High-density Lipoprotein-Cholesterol (mg/dl) | 36.7 mg/dL STANDARD_DEVIATION 7.4 | — |
| Plasma Triglyceride (mg/dl) | 127.6 mg/dL STANDARD_DEVIATION 80.4 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 27 participants | — |
| Sex: Female, Male Female | 14 Participants | — |
| Sex: Female, Male Male | 13 Participants | — |
| Systolic Blood Pressure (mmHg) | 120.5 mmHg STANDARD_DEVIATION 8.4 | — |
| Waist Circumference (cm) | 109.8 cm STANDARD_DEVIATION 12.2 | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 29 |
| other Total, other adverse events | 0 / 29 | 0 / 29 |
| serious Total, serious adverse events | 0 / 29 | 0 / 29 |
Outcome results
Endotoxin
Fasting serum endotoxin concentration
Time frame: Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Endotoxin | 21.2 EU/mL | Standard Deviation 3 |
| Potato Diet | Endotoxin | 23.3 EU/mL | Standard Deviation 3 |
Vascular Endothelial Function
Area under curve (change from baseline) for brachial artery flow-mediated dilation (FMD). The unit for FMD is %, which is calculated as: \[vessel diameter in millimeters (post-occlusion) - vessel diameter in millimeters (pre-occlusion)\] / vessel diameter in millimeters (pre-occlusion) x 100. FMD(%) is then used to caluclate area under the curve based on independent measures of FMD at 0-120 minutes)
Time frame: Day 14 Postprandial (0, 30, 60, 90, 120 minutes)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Vascular Endothelial Function | -259 % x min | Standard Error 75 |
| Potato Diet | Vascular Endothelial Function | -198 % x min | Standard Error 71 |
cIMT
Carotid intima-media thickness. Mean thickness of left and right carotid artery intima media.
Time frame: Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | cIMT | 0.603 mm | Standard Deviation 0.109 |
| Potato Diet | cIMT | 0.609 mm | Standard Deviation 0.114 |
Day 0 BMI
Body mass index calculated as kg weight per meters squared
Time frame: Day 0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Day 0 BMI | 35.6 kg/m^2 | Standard Error 1.2 |
| Potato Diet | Day 0 BMI | 35.7 kg/m^2 | Standard Error 1.2 |
Day 0 Diastolic Blood Pressure
Diastolic blood pressure on Day 0
Time frame: Day 0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Day 0 Diastolic Blood Pressure | 81.5 mmHg | Standard Error 1.3 |
| Potato Diet | Day 0 Diastolic Blood Pressure | 81.9 mmHg | Standard Error 1.5 |
Day 0 Systolic Blood Pressure
Systolic blood pressure on Day 0
Time frame: Day 0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Day 0 Systolic Blood Pressure | 123.1 mmHg | Standard Error 1.9 |
| Potato Diet | Day 0 Systolic Blood Pressure | 119.1 mmHg | Standard Error 2.2 |
Day 0 Waist Circumference
Waist circumference in centimeters
Time frame: Day 0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Day 0 Waist Circumference | 108.5 cm | Standard Error 2.2 |
| Potato Diet | Day 0 Waist Circumference | 119.1 cm | Standard Error 2.2 |
Day 14 BMI
Body mass index calculated as kg weight per meters squared
Time frame: Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Day 14 BMI | 35.1 kg/m^2 | Standard Error 1.1 |
| Potato Diet | Day 14 BMI | 35.2 kg/m^2 | Standard Error 1.1 |
Day 14 Diastolic Blood Pressure
Diastolic blood pressure on Day 14
Time frame: Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Day 14 Diastolic Blood Pressure | 75.9 mmHg | Standard Error 1.7 |
| Potato Diet | Day 14 Diastolic Blood Pressure | 77.7 mmHg | Standard Error 1.4 |
Day 14 Systolic Blood Pressure
Systolic blood pressure on Day 14
Time frame: Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Day 14 Systolic Blood Pressure | 113.6 mmHg | Standard Error 1.9 |
| Potato Diet | Day 14 Systolic Blood Pressure | 114.6 mmHg | Standard Error 1.8 |
Day 14 Waist Circumference
Waist circumference in centimeters
Time frame: Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Day 14 Waist Circumference | 107.8 mmHg | Standard Error 2.4 |
| Potato Diet | Day 14 Waist Circumference | 107.5 mmHg | Standard Error 2.4 |
Fasting Cholecystokinin
Fasting plasma concentration of CCK
Time frame: Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Fasting Cholecystokinin | 14.3 pmol/L | Standard Error 3.1 |
| Potato Diet | Fasting Cholecystokinin | 14.2 pmol/L | Standard Error 3.4 |
Fasting Endotoxin
Fasting serum endotoxin concentration
Time frame: Day 0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Fasting Endotoxin | 26.6 EU/mL | Standard Error 2 |
| Potato Diet | Fasting Endotoxin | 22.3 EU/mL | Standard Error 2.1 |
Fasting Glucose Day 0
Fasting plasma glucose
Time frame: Fasting glucose on Day 0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Fasting Glucose Day 0 | 104 mg/dL | Standard Deviation 13.5 |
| Potato Diet | Fasting Glucose Day 0 | 109.5 mg/dL | Standard Deviation 14.6 |
Fasting Glucose Day 14
Fasting plasma glucose Day 14
Time frame: Fasting glucose on Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Fasting Glucose Day 14 | 101.9 mg/dL | Standard Deviation 12.3 |
| Potato Diet | Fasting Glucose Day 14 | 102.3 mg/dL | Standard Deviation 13.5 |
Fasting Insulin Day 0
Fasting plasma insulin
Time frame: Fasting insulin on Day 0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Fasting Insulin Day 0 | 21.1 uIU/mL | Standard Error 5.5 |
| Potato Diet | Fasting Insulin Day 0 | 17.0 uIU/mL | Standard Error 2 |
Fasting Insulin Day 14
Fasting plasma insulin Day 14
Time frame: Fasting insulin on Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Fasting Insulin Day 14 | 14.2 uIU/mL | Standard Error 2 |
| Potato Diet | Fasting Insulin Day 14 | 14.9 uIU/mL | Standard Error 2.4 |
Fasting Malondialdehyde (MDA)
Fasting plasma MDA concentration, biomarker of oxidative stress
Time frame: Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Fasting Malondialdehyde (MDA) | 1.78 umol/L | Standard Error 0.1 |
| Potato Diet | Fasting Malondialdehyde (MDA) | 1.93 umol/L | Standard Error 0.1 |
Fasting NOx
Fasting plasma concentration of nitrite/nitrate
Time frame: Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Fasting NOx | 29.8 umol/L x min | Standard Error 3.7 |
| Potato Diet | Fasting NOx | 30.1 umol/L x min | Standard Error 2.3 |
Fasting Vascular Endothelial Function
Fasting flow-mediated dilation of the brachial artery. Measure is calculated as: \[post-occlusion vessel diameter (mm) - pre-occlusion vessel diameter (mm) / pre-occlusion vessel diameter (mm)\] x 100
Time frame: Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Fasting Vascular Endothelial Function | 7.2 % change in blood vessel dilation | Standard Error 1.3 |
| Potato Diet | Fasting Vascular Endothelial Function | 8.7 % change in blood vessel dilation | Standard Error 1.3 |
Fecal Acetate
Fecal concentration of acetate
Time frame: Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Fecal Acetate | 52.3 umol/g | Standard Error 4.7 |
| Potato Diet | Fecal Acetate | 46.6 umol/g | Standard Error 3.9 |
Fecal Butyrate
Fecal concentration of butyrate
Time frame: Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Fecal Butyrate | 21.3 umol/g | Standard Error 2.7 |
| Potato Diet | Fecal Butyrate | 17.9 umol/g | Standard Error 2.6 |
Fecal Propionate
Fecal concentration of propionate
Time frame: Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Fecal Propionate | 23.1 umol/g | Standard Error 2.2 |
| Potato Diet | Fecal Propionate | 19.3 umol/g | Standard Error 2.1 |
Lactulose/Mannitol Ratio
Urinary concentration of the non-digestible sugars lactulose/mannitol (mg/mg)
Time frame: Day 14, 0-5 hours post-consumption of sugar probes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Lactulose/Mannitol Ratio | .154 Ratio (mg/mg) | Standard Error 0.013 |
| Potato Diet | Lactulose/Mannitol Ratio | .151 Ratio (mg/mg) | Standard Error 0.1 |
Postprandial Cholecystokinin
Plasma CCK area under curve change from baseline
Time frame: Day 14 postprandial (0, 30, 60, 90, 120 minutes)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Postprandial Cholecystokinin | -196 pmol/L x min | Standard Error 266 |
| Potato Diet | Postprandial Cholecystokinin | -67 pmol/L x min | Standard Error 344 |
Postprandial Endotoxin
Postprandial serum endotoxin concentration area under curve change from baseline
Time frame: Day 14 postprandial (0, 30, 60, 90, 120 minutes)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Postprandial Endotoxin | 450 EU/ml x min | Standard Error 249 |
| Potato Diet | Postprandial Endotoxin | -120 EU/ml x min | Standard Error 176 |
Postprandial Glucose
Postprandial plasma glucose concentration area under curve change from baseline
Time frame: Day 14 postprandial (0, 30, 60, 90, 120 minutes)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Postprandial Glucose | 2649 mg/dL x min | Standard Error 499 |
| Potato Diet | Postprandial Glucose | 2808 mg/dL x min | Standard Error 565 |
Postprandial Insulin
Plasma insulin concentration area under curve change from baseline
Time frame: Day 14 postprandial (0, 30, 60, 90, 120 minutes)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Postprandial Insulin | 5940 uIU/mL x min | Standard Error 670 |
| Potato Diet | Postprandial Insulin | 7086 uIU/mL x min | Standard Error 1372 |
Postprandial Malondialdehyde (MDA)
Plasma MDA concentration, biomarker of oxidative stress area under curve change from baseline
Time frame: Day 14 postprandial (0, 30, 60, 90, 120 minutes)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Postprandial Malondialdehyde (MDA) | 57.2 umol/L x min | Standard Error 6.8 |
| Potato Diet | Postprandial Malondialdehyde (MDA) | 45.4 umol/L x min | Standard Error 7.2 |
Postprandial NOx
Plasma total nitrite/nitrate area under curve change from baseline
Time frame: Day 14 postprandial (0, 30, 60, 90, 120 minutes)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Postprandial NOx | -240 umol/L x min | Standard Error 88 |
| Potato Diet | Postprandial NOx | -433 umol/L x min | Standard Error 48 |
Sucralose/Erythritol Ratio
Urinary concentration of the non-digestible sugars sucralose/erythritol
Time frame: Day 14, 6-24 hours post-consumption of sugar probes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Sucralose/Erythritol Ratio | .0148 Ratio (mg/mg) | Standard Error 0.002 |
| Potato Diet | Sucralose/Erythritol Ratio | 0.01667 Ratio (mg/mg) | Standard Error 0.001925 |
Vitamin C
Fasting vitamin C concentration, biomarker of oxidative stress
Time frame: Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bagel Diet | Vitamin C | 47.5 umol/L | Standard Error 2.9 |
| Potato Diet | Vitamin C | 52.5 umol/L | Standard Error 4.8 |