Cheese Consumption and Human Microvascular Function

Phase 1

Completed

Conditions: Microvascular Dysfunction

Interventions: Drug: Acetylcholine (ACh) Dose Response
Drug: Local Heating (LH)
Drug: Flow Mediated Dilation with nitroglycerin

Registration Number: NCT03376555

Lead Sponsor: Lacy Alexander

Brief Summary: Increased dairy intake is associated with improved measures of blood vessel health. Dairy cheese, however, is often high in sodium. Dietary sodium can impair blood vessel function. The researchers examine if and how natural cheese may protect against impairments in blood vessel function caused by sodium. For this study, participants complete four 8-day controlled feeding periods in which they eat cheese (6 oz/day) or no cheese during a low-sodium or high-sodium base-diet. The participants complete baseline experiments while on their normal personal diet and then repeat experiments at the end of each controlled feeding period. In some of our experiments, the researchers use a technique called "microdialysis" (MD). With MD, the researchers perfuse some research drugs into the skin on the forearm through tiny tubing that mimics capillaries. These MD drugs mimic or block substances the body naturally makes to control the small blood vessels in the skin. The drugs remain in nickel-sized areas around the tubing and do not go into the rest of the body. The researchers also use a standard technique called "flow mediated dilation" (FMD) that uses blood pressure cuffs and ultrasound to look at the health of larger blood vessels in the body. FMD includes placing a small tablet of nitroglycerin under the tongue during part of the test.

Detailed Description: Subject screening will be performed by the Penn State Clinical Translational Research Center (CTRC) medical staff and will include a physical exam by a clinician, anthropometry, and a chemical and lipid profile, liver and renal function. Participants meet with a registered dietitian to determine their caloric energy requirements and identify food preferences. The interview includes surveying the subject's physical activity over the previous 7 days.

Subjects will undergo baseline microdialysis experiments to examine the function of the blood vessels in the skin microcirculation. Subjects will also go through a baseline assessment of conduit vessel endothelial and vascular smooth muscle function with brachial artery flow-mediated vasodilation (FMD), and sublingual nitroglycerin. Following baseline experiments, subjects participate in 4 controlled feeding periods, each 8 days in duration. The controlled feeding periods are assigned in a randomized order. At the end of each 8-day controlled dietary period, subjects will repeat microdialysis experiments, brachial artery FMD, and responsiveness to sublingual nitroglycerin.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 13

Inclusion Criteria

Seated systolic pressure 120-140 mmHg
Seated diastolic pressure 70-90 mmHg.
Normoglycemic (HbA1C <5.7%)

Exclusion Criteria

Taking pharmacotherapy that alters peripheral vascular control
Pregnancy
Breastfeeding
Females taking contraceptives (pills, patches, shots, etc.) or hormone replacement therapy
Taking illicit and/or recreational drugs
Use of nicotine containing-products (e.g. smoking, chewing tobacco, etc.)
Known allergy to latex or investigative substances

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Baseline	Acetylcholine (ACh) Dose Response	Subjects on normal personal diet Acetylcholine (ACh) Dose Response, Local heating (LH), and Flow Mediated Dilation with nitroglycerin experiments
Low Sodium, No Cheese	Acetylcholine (ACh) Dose Response	Diet contains 1,500 mg sodium per day Diet does not contain dairy cheese After 8 days on diet: Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments
Low Sodium, Cheese	Acetylcholine (ACh) Dose Response	Diet contains 1,500 mg sodium per day Diet contains 6 oz dairy cheese per day After 8 days on diet: Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments
High Sodium, Cheese	Flow Mediated Dilation with nitroglycerin	Diet contains 5,500 mg sodium per day Diet contains 6 oz dairy cheese per day After 8 days on diet: Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments
Baseline	Local Heating (LH)	Subjects on normal personal diet Acetylcholine (ACh) Dose Response, Local heating (LH), and Flow Mediated Dilation with nitroglycerin experiments
Baseline	Flow Mediated Dilation with nitroglycerin	Subjects on normal personal diet Acetylcholine (ACh) Dose Response, Local heating (LH), and Flow Mediated Dilation with nitroglycerin experiments
Low Sodium, No Cheese	Local Heating (LH)	Diet contains 1,500 mg sodium per day Diet does not contain dairy cheese After 8 days on diet: Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments
Low Sodium, No Cheese	Flow Mediated Dilation with nitroglycerin	Diet contains 1,500 mg sodium per day Diet does not contain dairy cheese After 8 days on diet: Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments
Low Sodium, Cheese	Local Heating (LH)	Diet contains 1,500 mg sodium per day Diet contains 6 oz dairy cheese per day After 8 days on diet: Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments
Low Sodium, Cheese	Flow Mediated Dilation with nitroglycerin	Diet contains 1,500 mg sodium per day Diet contains 6 oz dairy cheese per day After 8 days on diet: Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments
High Sodium, No Cheese	Acetylcholine (ACh) Dose Response	Diet contains 5,500 mg sodium per day Diet does not contain dairy cheese After 8 days on diet: Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments
High Sodium, No Cheese	Local Heating (LH)	Diet contains 5,500 mg sodium per day Diet does not contain dairy cheese After 8 days on diet: Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments
High Sodium, No Cheese	Flow Mediated Dilation with nitroglycerin	Diet contains 5,500 mg sodium per day Diet does not contain dairy cheese After 8 days on diet: Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments
High Sodium, Cheese	Acetylcholine (ACh) Dose Response	Diet contains 5,500 mg sodium per day Diet contains 6 oz dairy cheese per day After 8 days on diet: Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments
High Sodium, Cheese	Local Heating (LH)	Diet contains 5,500 mg sodium per day Diet contains 6 oz dairy cheese per day After 8 days on diet: Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments

Primary Outcome Measures

Name	Time	Method
Microvascular Reactivity to Acetylcholine	1 hour	Skin blood flow is measured with laser Doppler flowmetry (flux units) and normalized to cutaneous vascular conductance by dividing by mean arterial pressure. Log molar increasing concentrations of acetylcholine are perfused and dose response curves are generated. Dose response curves were analyzed to determine the logEC50 (log Molar)

Secondary Outcome Measures

Name	Time	Method
Flow Mediated Dilation	8 days	Flow mediated dilation is measured through Doppler ultrasound probe placed at brachial artery.
Systolic Blood Pressure	8 days	Blood pressure is measured via brachial auscultation manually or with a critical care monitor. The peak blood pressure during a cardiac cycle when the heart contracts.
Diastolic Blood Pressure	8 days	Blood pressure is measured via brachial auscultation manually or with a critical care monitor. The lowest blood pressure during a cardiac cycle when the heart is between beats.