Regulation of Postprandial Nitric Oxide Bioavailability and Vascular Function By Dairy Milk

Ohio State University23 enrolled

Overview

Cardiovascular disease (CVD) is the leading cause of death in the United States. Short-term increases in blood sugar, or postprandial hyperglycemia (PPH), affect blood vessel function and increase the risk of CVD. Greater intakes of dairy foods have been associated with a lower risk of CVD, but whether these effects occur directly or indirectly by displacing foods in the diet that might increase CVD risk is unclear. The health benefits of dairy on heart health are at least partly attributed to its ability to limit PPH and resulting PPH-mediated responses leading to vascular dysfunction. This provides rationale to further investigate dairy as a dietary strategy to reduce PPH and risk for CVD. The objective of this study is to define the extent to which dairy milk, and its whey and casein protein fractions, protect against postprandial vascular dysfunction by reducing oxidative stress responses that limit nitric oxide bioavailability to the vascular endothelium in adults with prediabetes.

This study consists of four, 3-hour postprandial trials in response to consuming the following dietary treatments: 1. oral glucose challenge, 2. oral glucose challenge in combination with non-fat milk, 3. oral glucose challenge in combination with whey protein isolate, and 4. oral glucose challenge in combination with sodium caseinate. For three days preceding each trial, participants will be provided all meals to standardize physiologic responses to test meals. On each trial day, vascular function will be assessed and blood samples collected prior to and at 30 minute intervals for 3 hours following test meal ingestion.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Interventions

GlucoseOTHER

Following baseline measurements, participants will consume a 75 g glucose solution within five minutes.

Glucose with Non-fat MilkOTHER

Following baseline measurements, participants will consume 75 g glucose dissolved in two cups of non-fat milk within five minutes.

Glucose with Whey Protein IsolateOTHER

Following baseline measurements, participants will consume 75 g glucose and whey protein isolate dissolved in 2 cups water within five minutes.

Glucose with Sodium CaseinateOTHER

Following baseline measurements, participants will consume 75 g glucose and sodium caseinate dissolved in 2 cups water within five minutes.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. hemoglobin A1c 5.7-6.4% 2. non-dietary supplement user 3. no medications affecting vasodilation, inflammation, or energy metabolism 4. no CVD 5. nonsmokers 6. individuals having blood pressure \<140/90 mmHg and total cholesterol \<240 mg/dL Exclusion Criteria: 1. unstable weight (±2 kg) 2. vegetarian or dairy allergy 3. alcohol intake \>3 drinks/day or \>10 drinks/week 4. ≥7 hours/week of aerobic activity

Outcomes

Primary Outcomes

Vascular Endothelial Function

Flow mediated dilation (FMD) of the brachial artery, calculated as FMD AUC for 0-180 minutes (change from baseline)

Time frame: Area under curve for FMD for three hours (0, 30, 60, 90, 120, 180 minutes)

Secondary Outcomes

Nitrite/Nitrate (NOx)

NOx AUC for 0-180 minutes

Time frame: Area under curve for nitrite/nitrate for three hours (0, 30, 60, 90, 120, 180 min) (change from baseline)

Plasma Glucose

Plasma glucose concentration from 0-180 minutes

Time frame: Area under the curve for glucose for three hours (0, 30, 60, 90, 120, 180 minutes) (change from baseline)

Malondialdehyde (MDA)

Plasma MDA measured as MDA AUC from 0-180 minutes

Time frame: Area under curve for MDA for three hours (0, 30, 60, 90, 120, 150, 180 min.) (change from baseline)

Arginine (ARG)

Plasma arginine concentration, calculated as ARG AUC from 0-180 minutes

Time frame: ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)

Asymmetric Dimethylarginine/Arginine (ADMA/ARG)

Plasma ADMA/arginine concentration, calculated as ADMA/ARG AUC from 0-180 minutes

Time frame: ADMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)

Symmetric Dimethylarginine/Arginine (SDMA/ARG)

Plasma SDMA/arginine concentration, calculated as SDMA/ARG AUC from 0-180 minutes

Time frame: SDMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)

Tetrahydrobiopterin/Dihydrobiopterin (BH4/BH2)

Plasma BH4/BH2 concentration, calculated as BH4/BH2 AUC from 0-180 minutes

Time frame: Plasma BH4/BH2 concentration area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)

Insulin

Plasma insulin concentration, calculated as insulin AUC from 0-180 minutes

Time frame: Insulin area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)

Cholecystokinin (CCK)

Plasma CCK concentration, calculated as CCK AUC from 0-180 minutes

Time frame: CCK area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)

8-isoprostaglandin-F2a

Plasma 8-isoprostaglandin-F2a concentration, calculated as 8-isoprostaglandin-F2a AUC from 0-180 minutes

Time frame: 8-isoprostaglandin-F2a area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)

8-isoprostaglandin-F2a/Arachidonic Acid

Plasma 8-isoprostaglandin-F2a/Arachidonic acid concentration, calculated as 8-isoprostaglandin-F2a/Arachidonic acid AUC from 0-180 minutes

Time frame: 8-isoprostaglandin-F2a/Arachidonic acid area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)

Arachidonic Acid

Arachidonic acid concentration, calculated as Arachidonic acid AUC from 0-180 minutes

Time frame: Arachidonic acid area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)