Cheese Consumption and Human Microvascular Function

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.

Study Overview

• Status: Completed
• Conditions: Microvascular Dysfunction
• Intervention / Treatment: Dietary supplement: Low sodium no cheese; Dietary supplement: Low sodium cheese; Dietary supplement: High sodium no cheese; Dietary supplement: High sodium cheese

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • University Park, Pennsylvania, United States, 16802
      • Pennsylvania State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Impact of Dairy and Sodium on Microvascular Health; Cross over design with a baseline and 4 dietary interventions

Dietary supplement: Low sodium no cheese; Diet contains 1,500 mg sodium per day Diet does not contain dairy cheese 8 days; Dietary supplement: Low sodium cheese; Diet contains 1,500 mg sodium per day Diet contains 6 oz dairy cheese per day 8 days; Dietary supplement: High sodium no cheese; Diet contains 5,500 mg sodium per day Diet does not contain dairy cheese 8 days; Dietary supplement: High sodium cheese; Diet contains 5,500 mg sodium per day Diet contains 6 oz dairy cheese per day 8 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microvascular Reactivity to Acetylcholine	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)	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic Blood Pressure	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.	8 days
Diastolic Blood Pressure	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.	8 days
Flow Mediated Dilation	Flow mediated dilation is measured through Doppler ultrasound probe placed at brachial artery.	8 days

Collaborators and Investigators

• Sponsor: Lacy Alexander
• Collaborators: National Dairy Council
• Investigators: Principal Investigator: Lacy M Alexander, PhD, Penn State University

Publications and helpful links

General Publications

• Alba BK, Stanhewicz AE, Dey P, Bruno RS, Kenney WL, Alexander LM. Controlled Feeding of an 8-d, High-Dairy Cheese Diet Prevents Sodium-Induced Endothelial Dysfunction in the Cutaneous Microcirculation of Healthy, Older Adults through Reductions in Superoxide. J Nutr. 2020 Jan 1;150(1):55-63. doi: 10.1093/jn/nxz205.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: December 13, 2017
• First Submitted That Met QC Criteria: December 13, 2017
• First Posted (Actual): December 18, 2017

Study Record Updates

• Last Update Posted (Actual): May 4, 2025
• Last Update Submitted That Met QC Criteria: May 2, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Hypertension; Cardiovascular Disease; Skin; Oxidative Stress; Dairy; Diet; Cheese; Blood Pressure; Sodium; Microcirculation; Nitric Oxide; Nitroglycerin; Superoxide; Flow Mediated Vasodilation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Cholinergic Agents; Cholinergic Agonists; Nitroglycerin; Acetylcholine
• Other Study ID Numbers: STUDY4340; 129552 (Other Identifier: FDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No