Hypercholesterolemia, Hypertension
Conditions
Keywords
Blood Pressure; Lipids; Dietary Protein
Brief summary
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.
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.
Interventions
DIETARY_SUPPLEMENTSoy 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
DIETARY_SUPPLEMENTMilk 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.
DIETARY_SUPPLEMENTCarbohydrate-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.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Tulane University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The randomization assignment list was generated by a computer program that could only be accessed by the study data coordinator. Apart from the data coordinator, all research personnel, including investigators, study coordinators, and BP technicians, and the study participants were unaware of treatment assignment.
Intervention model description
The trial participants were assigned to take 40 g/d soy protein, milk protein, or carbohydrate supplementation each for 8 weeks in a random order. A 3-week washout period was implemented between the interventions.
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Systolic Blood Pressure at 8 Weeks | Baseline and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body Weight at 8 Weeks | Baseline and 8 Weeks | Body weight was measured by trained staff using a standard protocol at week 8. |
| Change From Baseline in Serum LDL-cholesterol at 8 Weeks | Baseline and 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 117 |
| 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. | 117 |
| 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. | 118 |
| Total | 352 |
Baseline characteristics
| Characteristic | Soy Protein-milk Protein-carbohydrate | Milk Protein-carbohydrate-soy Protein | Carbohydrate-soy Protein-milk Protein | Total |
|---|---|---|---|---|
| Age, Continuous | 48.4 years STANDARD_DEVIATION 11.5 | 46.7 years STANDARD_DEVIATION 10.7 | 48.1 years STANDARD_DEVIATION 8.7 | 47.7 years STANDARD_DEVIATION 10.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 39 Participants | 38 Participants | 44 Participants | 121 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 78 Participants | 79 Participants | 74 Participants | 231 Participants |
| Region of Enrollment United States | 117 participants | 117 participants | 118 participants | 352 participants |
| Sex: Female, Male Female | 48 Participants | 49 Participants | 50 Participants | 147 Participants |
| Sex: Female, Male Male | 69 Participants | 68 Participants | 68 Participants | 205 Participants |
| Systolic Blood Pressure | 127.2 mmHg STANDARD_DEVIATION 9.3 | 126.7 mmHg STANDARD_DEVIATION 11 | 126.1 mmHg STANDARD_DEVIATION 9.7 | 126.7 mmHg STANDARD_DEVIATION 10 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 352 | 0 / 352 | 0 / 352 |
| other Total, other adverse events | 0 / 352 | 0 / 352 | 0 / 352 |
| serious Total, serious adverse events | 0 / 352 | 0 / 352 | 0 / 352 |
Outcome results
Primary
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.
Time frame: Baseline and 8 Weeks
Population: We conducted analysis according to intention-to-treat principle. All participants with data were included in analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Soy Protein Supplementation | Change From Baseline in Average Systolic Blood Pressure at 8 Weeks | -1.5 mmHg |
| Milk Protein Supplementation | Change From Baseline in Average Systolic Blood Pressure at 8 Weeks | -1.8 mmHg |
| Carbohydrate Supplementation | Change From Baseline in Average Systolic Blood Pressure at 8 Weeks | 0.5 mmHg |
Secondary
Body Weight at 8 Weeks
Body weight was measured by trained staff using a standard protocol at week 8.
Time frame: Baseline and 8 Weeks
Population: All participants with body weight measures at each intervention phase
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Soy Protein Supplementation | Body Weight at 8 Weeks | 86.2 kg |
| Milk Protein Supplementation | Body Weight at 8 Weeks | 86.6 kg |
| Carbohydrate Supplementation | Body Weight at 8 Weeks | 86.7 kg |
Secondary
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.
Time frame: Baseline and 8 Weeks
Population: All participants with lipid data
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Soy Protein Supplementation | Change From Baseline in Serum LDL-cholesterol at 8 Weeks | -3.97 mg/dL |
| Milk Protein Supplementation | Change From Baseline in Serum LDL-cholesterol at 8 Weeks | -2.56 mg/dL |
| Carbohydrate Supplementation | Change From Baseline in Serum LDL-cholesterol at 8 Weeks | -1.41 mg/dL |