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Cheese Consumption and Human Microvascular Function

Cheese Consumption and Human Microvascular Function

Status
Completed
Phases
Phase 1Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03376555
Enrollment
13
Registered
2017-12-18
Start date
2017-07-01
Completion date
2021-03-01
Last updated
2025-05-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Microvascular Dysfunction

Keywords

Sodium, Hypertension, Blood Pressure, Cardiovascular Disease, Nitric Oxide, Skin, Dairy, Cheese, Oxidative Stress, Diet, Flow Mediated Vasodilation, Nitroglycerin, Superoxide, Microcirculation

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.

Interventions

DIETARY_SUPPLEMENTLow sodium no cheese

Diet contains 1,500 mg sodium per day Diet does not contain dairy cheese 8 days

DIETARY_SUPPLEMENTLow sodium cheese

Diet contains 1,500 mg sodium per day Diet contains 6 oz dairy cheese per day 8 days

DIETARY_SUPPLEMENTHigh sodium no cheese

Diet contains 5,500 mg sodium per day Diet does not contain dairy cheese 8 days

DIETARY_SUPPLEMENTHigh sodium cheese

Diet contains 5,500 mg sodium per day Diet contains 6 oz dairy cheese per day 8 days

Sponsors

National Dairy Council
CollaboratorOTHER
Lacy Alexander
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE

Masking description

Investigator and Outcomes Assessor are masked according to treatment.

Intervention model description

All subjects participate in 4 diets in randomized order. The diets differ in the amount of sodium and dairy cheese content. Each diet is consumed for 8 days. Minimum washout of 1 week between diets. Baseline experiment is conducted prior to first dietary intervention, and the experiment is repeated after each dietary intervention.

Eligibility

Sex/Gender
ALL
Age
55 Years to 75 Years
Healthy volunteers
Yes

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

Design outcomes

Primary

MeasureTime frameDescription
Microvascular Reactivity to Acetylcholine1 hourSkin 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

MeasureTime frameDescription
Systolic Blood Pressure8 daysBlood 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 Pressure8 daysBlood 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.
Flow Mediated Dilation8 daysFlow mediated dilation is measured through Doppler ultrasound probe placed at brachial artery.

Countries

United States

Participant flow

Recruitment details

July 2017 to October 2019, Centre County, PA

Pre-assignment details

Subjects were enrolled in 4 separate 8-d controlled feeding interventions in a randomized, crossover study design. All food and beverages were prepared by a registered dietitian in the Pennsylvania State Clinical Research Center Metabolic Kitchen. Investigators involved in data collection and analysis were blinded to the dietary treatment.

Participants by arm

ArmCount
Sodium and Dairy Interventions
low sodium no cheese low sodium cheese high sodium no cheese high sodium cheese baseline
13
Total13

Baseline characteristics

CharacteristicSodium and Dairy Interventions
Age, Customized
age
64 years
STANDARD_DEVIATION 2
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
0 Participants
Race (NIH/OMB)
Black or African American
0 Participants
Race (NIH/OMB)
More than one race
0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
Race (NIH/OMB)
White
13 Participants
Region of Enrollment
United States
13 participants
Sex: Female, Male
Female
7 Participants
Sex: Female, Male
Male
6 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
deaths
Total, all-cause mortality
0 / 110 / 110 / 110 / 110 / 11
other
Total, other adverse events
0 / 110 / 110 / 110 / 110 / 11
serious
Total, serious adverse events
0 / 110 / 110 / 110 / 110 / 11

Outcome results

Primary

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)

Time frame: 1 hour

Population: Data were collected with Windaq (Dataq Instruments) at a frequency of 40 Hz. CVC was calculated as red blood cell flux,. ACh dose concentrations were log-transformed and CVC was expressed as a percentage of maximum. Pharmacological curve modeling was performed using a 4-parameter, nonlinear regression with a variable slope to detect between-diet differences in microvascular sensitivity logEC50 (log Molar) of the group mean curve\] to ACh.

ArmMeasureValue (MEAN)Dispersion
BaselineMicrovascular Reactivity to Acetylcholine-4.90 log (M)Standard Error 0.2
Low Sodium, No CheeseMicrovascular Reactivity to Acetylcholine-4.82 log (M)Standard Error 0.2
Low Sodium, CheeseMicrovascular Reactivity to Acetylcholine-5.44 log (M)Standard Error 0.2
High Sodium, No CheeseMicrovascular Reactivity to Acetylcholine-3.21 log (M)Standard Error 0.55
High Sodium, CheeseMicrovascular Reactivity to Acetylcholine-3.21 log (M)Standard Error 0.55
Secondary

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.

Time frame: 8 days

ArmMeasureValue (MEAN)Dispersion
BaselineDiastolic Blood Pressure81 mmHgStandard Error 1
Low Sodium, No CheeseDiastolic Blood Pressure75 mmHgStandard Error 1
Low Sodium, CheeseDiastolic Blood Pressure74 mmHgStandard Error 1
High Sodium, No CheeseDiastolic Blood Pressure78 mmHgStandard Error 1
High Sodium, CheeseDiastolic Blood Pressure76 mmHgStandard Error 1
Secondary

Flow Mediated Dilation

Flow mediated dilation is measured through Doppler ultrasound probe placed at brachial artery.

Time frame: 8 days

ArmMeasureValue (MEAN)Dispersion
BaselineFlow Mediated Dilation3.78 percentage of flow mediated vasodilationStandard Error 0.78
Low Sodium, No CheeseFlow Mediated Dilation5.07 percentage of flow mediated vasodilationStandard Error 0.9
Low Sodium, CheeseFlow Mediated Dilation4.20 percentage of flow mediated vasodilationStandard Error 0.76
High Sodium, No CheeseFlow Mediated Dilation3.45 percentage of flow mediated vasodilationStandard Error 1.04
High Sodium, CheeseFlow Mediated Dilation5.90 percentage of flow mediated vasodilationStandard Error 1.34
Secondary

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.

Time frame: 8 days

ArmMeasureValue (MEAN)Dispersion
BaselineSystolic Blood Pressure125 mmHgStandard Error 1
Low Sodium, No CheeseSystolic Blood Pressure122 mmHgStandard Error 2
Low Sodium, CheeseSystolic Blood Pressure121 mmHgStandard Error 3
High Sodium, No CheeseSystolic Blood Pressure127 mmHgStandard Error 3
High Sodium, CheeseSystolic Blood Pressure124 mmHgStandard Error 3

Source: ClinicalTrials.gov · Data processed: Feb 28, 2026