Clinical Trial of Protein and Blood Pressure (ProBP)

The purpose of this randomized, double-blind, controlled trial is to examine the effect of soybean protein supplementation on blood pressure in persons with prehypertension or stage-1 hypertension.

Study Overview

• Status: Completed
• Conditions: Hypertension; Hypercholesterolemia
• Intervention / Treatment: Dietary supplement: Soy protein-milk protein-carbohydrate; Dietary supplement: Milk protein-carbohydrate-soy protein; Dietary supplement: Carbohydrate-soy protein-milk protein

Detailed Description

Background: Epidemiologic studies suggest that vegetable protein intake is inversely related to blood pressure.

Objectives: To examine the effect of soybean protein supplementation on blood pressure in persons with prehypertension or stage-1 hypertension

Design: Randomized, double-blind, controlled trial

Study Participants: 350 participants, aged 35-64 years, with an initial untreated systolic blood pressure of 130-159 mmHg and/or diastolic blood pressure of 80-99 mmHg

Intervention: Study participants will be randomly assigned to take 40-grams of isolated soybean protein supplements per day or complex carbohydrate control for 12 weeks.

Outcomes: Blood pressure measurements will be obtained using random-zero sphygmomanometers at baseline and during the trial at weeks 6 and 12. Net changes in systolic and diastolic blood pressure before and after the intervention is the primary outcome.

• Study Type: Interventional
• Enrollment (Actual): 352
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Systolic BP of 120 to 159 mm Hg and diastolic BP of 80 to 95 mm Hg (average of 6 measurements at 2 screening visits)
2. Willing to participate in all aspects of the study

Exclusion Criteria:

1. Consumption of dietary protein greater than or equal to 1.63 grams/kg per day, as determined by two 24-hour dietary recalls
2. Stage-2 or higher severe hypertension (systolic BP greater than or equal to 160 mm Hg and/or diastolic BP greater than or equal to 95 mm Hg)
3. Use of antihypertensive medications or medications that affect BP
4. History of clinical heart disease (e.g., angina/heart attack, coronary revascularization, heart failure, stroke/transient ischemic attack, peripheral arterial disease)
5. Kidney disease (serum creatinine level greater than or equal to 1.7 mg/dL for men and greater than or equal to 1.5 mg/dL for women)
6. Current hypercholesterolemia (fasting serum total cholesterol greater than or equal to 240 mg/dL) or use of cholesterol-lowering medications
7. Current diabetes (fasting serum glucose greater than or equal to 126 mg/dL) or use of insulin or oral hypoglycemic agents
8. Severe obesity (body mass index greater than or equal to 40 kg/m²)
9. Current use of prescription weight loss medications, underwent weight loss surgery, and/or experienced weight loss greater than 15 pounds within the 6 months prior to study entry
10. Cancer (except non-melanoma skin cancer) that required treatment during the year prior to study entry
11. Consumption of more than 14 alcoholic beverages per week
12. Current participation in another medical study
13. Consumption of milk or soy protein greater than or equal to the 90th percentile of intake in the U.S. general population
14. Has another member of the household participating in the study
15. Study employees or living with study employees
16. Allergy or intolerance to soy protein or milk protein products
17. Allergy to aspartame
18. Plans to move out of the study area (greater than or equal to 50 miles from the study site) and has difficulty coming to the study site
19. Inability or unwillingness to cooperate during the screening visits
20. Poor compliance during the screening period (intake of less than 85% of supplements)
21. Pregnant or plans to become pregnant during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Soy protein-milk protein-carbohydrate; Participants received 40 grams of soy protein daily for 8 weeks, 40 grams of milk protein daily for 8 weeks, and 40 grams of carbohydrate daily for 8 weeks.	Dietary supplement: Soy protein-milk protein-carbohydrate; 40 grams of soy protein per day for 8 weeks, 40 grams of milk protein per day for 8 weeks, and 40 grams of carbohydrate per day for 8 weeks
Active Comparator: Milk protein-carbohydrate-soy protein; Participants received 40 grams of milk protein daily for 8 weeks, 40 grams of carbohydrate daily for 8 weeks, and 40 grams of soy protein daily for 8 weeks.	Dietary supplement: Milk protein-carbohydrate-soy protein; 40 grams of milk protein per day for 8 weeks, 40 grams of carbohydrate per day for 8 weeks, 40 grams of soy protein per day for 8 weeks.
Active Comparator: Carbohydrate-soy protein-milk protein; Participants received 40 grams of complex carbohydrate daily for 8 weeks, 40 grams of soy protein daily for 8 weeks, and 40 grams of milk protein daily for 8 weeks.	Dietary supplement: Carbohydrate-soy protein-milk protein; 40 grams of carbohydrate per day for 8 weeks, 40 grams of soy protein per day for 8 weeks, 40 grams of milk protein per day for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Average Systolic Blood Pressure at 8 Weeks	The change of systolic blood pressure was calculated as the mean of 6 blood pressure values from two 8-week visits minus the mean of 6 values from 2 baseline visits within each intervention phase. At each visit, 3 BP values were measured with a Hawksley random-zero sphygmomanometer by trained and certified observers who were masked to group assignment. BP readings were taken from the right arm with appropriately sized cuffs after the participant had been seated quietly for 5 minutes. The participant was instructed not to eat, smoke, drink alcohol, or exercise for at least 30 minutes before their BP measurements.	Baseline and 8 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Serum LDL-cholesterol at 8 Weeks	Change in serum LDL-cholesterol was calculated as LDL-cholesterol at 8 weeks minus LDL-cholesterol at baseline. Over-night fasting serum LDL-cholesterol was measured with an enzymatic method.	Baseline and 8 Weeks
Body Weight at 8 Weeks	Body weight was measured by trained staff using a standard protocol at week 8.	Baseline and 8 Weeks

Collaborators and Investigators

• Sponsor: Tulane University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

General Publications

• Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005 Jan 15-21;365(9455):217-23. doi: 10.1016/S0140-6736(05)17741-1.
• He J, Wofford MR, Reynolds K, Chen J, Chen CS, Myers L, Minor DL, Elmer PJ, Jones DW, Whelton PK. Effect of dietary protein supplementation on blood pressure: a randomized, controlled trial. Circulation. 2011 Aug 2;124(5):589-95. doi: 10.1161/CIRCULATIONAHA.110.009159. Epub 2011 Jul 18.
• Wofford MR, Rebholz CM, Reynolds K, Chen J, Chen CS, Myers L, Xu J, Jones DW, Whelton PK, He J. Effect of soy and milk protein supplementation on serum lipid levels: a randomized controlled trial. Eur J Clin Nutr. 2012 Apr;66(4):419-25. doi: 10.1038/ejcn.2011.168. Epub 2011 Sep 28.
• Rebholz CM, Reynolds K, Wofford MR, Chen J, Kelly TN, Mei H, Whelton PK, He J. Effect of soybean protein on novel cardiovascular disease risk factors: a randomized controlled trial. Eur J Clin Nutr. 2013 Jan;67(1):58-63. doi: 10.1038/ejcn.2012.186. Epub 2012 Nov 28.

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: April 7, 2005
• First Submitted That Met QC Criteria: April 7, 2005
• First Posted (Estimate): April 8, 2005

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 10, 2023
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Blood Pressure; Lipids; Dietary Protein
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Caseins
• Other Study ID Numbers: H0330; R01HL068057 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

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