Subgroup analyses showed smaller sample s reporting larger effect sizes ; intervention lasting less than 6 months showed larger effect sizes and intention-to-treat analysis showed smaller effect sizes Lifestyle interventions may be of value in preventing and reducing blood pressure in LMICs .
Despite the overwhelming evidence supporting the effectiveness of antihypertensive medication , hypertension remains poorly controlled in low and middle-income countries ( LMICs ) .
Effect of Soybean Protein on Blood Pressure: A Randomized, Controlled Trial
Context Observational studies suggest that higher intake of vegetable protein is associated with lower blood pressures . Contribution This double-blind trial from China r and omly assigned 302 adults with high-normal or mildly elevated blood pressures ( diastolic blood pressure of 80 to 99 mm Hg , systolic blood pressure of 130 to 159 mm Hg , or both ) to daily cookies containing 40 g of either soybean protein or complex carbohydrates . At 12 weeks , soybean cookies reduced diastolic and systolic blood pressure values by about 3 to 4 mm Hg more than did the carbohydrate cookies . Caution s The follow-up duration was short . Implication s Soybean protein supplementation might help lower blood pressure in some people . The Editors Hypertension has become a global public health challenge , affecting approximately 50 million individuals in the United States and 1 billion individuals worldwide ( 1 , 2 ) . The prevalence of hypertension has increased dramatically in developing countries during the past several decades ( 1 , 3 ) and has increased slightly in the United States according to a recent national survey ( 4 ) . Hypertension is not only very common but is also an important major modifiable risk factor for cardiovascular disease , stroke , and chronic kidney disease ( 5 - 7 ) . Lifestyle modification , including nutritional intervention , provides an important approach for preventing and treating hypertension ( 2 , 8) . Clinical trials have documented that weight loss , exercise , alcohol restriction , sodium reduction , and potassium supplementation reduce blood pressure in both hypertensive and prehypertensive persons ( 2 , 8) . The effect of dietary macronutrients on blood pressure has not been well studied , although clinical trials indicate that diets rich in fruits , vegetables , and low-fat dairy products and with reduced saturated and total fat ( Dietary Approaches to Stop Hypertension [ DASH ] diet ) lower blood pressure ( 9 ) . Several epidemiologic studies have observed an inverse relationship between dietary protein intake and blood pressure ( 10 - 14 ) . The few clinical trials that examined the effect of an increased intake of dietary protein on blood pressure produced conflicting results ( 10 , 15 , 16 ) . In most of these trials , change in blood pressure was not the primary outcome of interest , the sample size was small , and only a single blood pressure measurement was obtained at the baseline and termination visits ( 10 ) . We conducted a r and omized , double-blind , controlled multicenter trial to test the effect of soybean protein supplementation on systolic and diastolic blood pressure among individuals with prehypertension or stage 1 hypertension in 3 sample s of community residents in the People 's Republic of China . Methods Our study was a r and omized , double-blind , complex carbohydratecontrolled multicenter clinical trial design ed to test the efficacy of 40 g of isolated soybean protein supplementation per day in lowering systolic and diastolic blood pressure  among individuals with prehypertension or stage 1 hypertension . Three clinical centers in the People 's Republic of China , located in Beijing , Xiulo ( Hebei province ) , and Wuhan ( Hubei province ) , participated in the trial . Demographic characteristics and lifestyle , including dietary habits , were similar in the 3 communities . In Beijing , the clinical center used a 2 2 factorial design to assign the study participants to soybean protein and potassium ( 60 mmol/d ) interventions ( 17 ) . The other 2 centers used a 2-group parallel design to assign the study participants to soybean protein supplements or a complex carbohydrate control . Investigators obtained informed consent before the initial screening visit and before r and omization . The institutional review boards at the Tulane University Health Sciences Center and the Cardiovascular Institute of the Chinese Academy of Medical Sciences approved the protocol . Study Participants Trial participants were men and women 35 to 65 years of age who had an average systolic blood pressure of 130 to 159 mm Hg , diastolic blood pressure of 80 to 99 mm Hg , or both based on an average of 9 readings ( 3 observations at each of 3 screening visits ) . The criteria for exclusion were self-reported use of antihypertensive medications in the previous 2 months ; a history of cardiovascular disease , diabetes mellitus , cancer , chronic obstructive pulmonary disease , psychiatric disease , or any other serious life-threatening illness that required regular medical treatment ; serum creatinine level of 150.3 mol/L or greater ( 1.7 mg/dL ) at the screening examination ; or alcohol intake of 21 drinks or more per week or at least 40 g/d . We also excluded women who were pregnant or who intended to become pregnant during the study . The study sites conducted community-based blood pressure prescreening to recruit the trial participants . We invited 862 persons who met blood pressure and other criteria at prescreening and who were willing to participate in the trial to the study clinics for screening visits . Of them , 302 persons met all eligibility criteria and were r and omly assigned ( Figure 1 ) . Of the 302 trial participants , 150 were recruited from Beijing , 84 were recruited from Hebei province , and 68 were recruited from Hubei province . Figure 1 . Study participant flow chart . Intervention We r and omly allocated 150 study participants to soybean protein supplementation and 152 study participants to the control group by using a computer-generated scheme . We stratified the r and omization by clinical site and used a block size of 4 . We also stratified the r and omization by potassium supplementation allocation at the Beijing clinical site , result ing in an equal proportion of study participants receiving potassium intervention in the  soybean protein supplement group ( 37 of 74 participants ) and the  control group ( 38 of 76 participants ) . An effect of an interaction between soybean protein and potassium supplementation on blood pressure was not evident . The r and omization assignment schedule was concealed in an ordered set of sealed envelopes , which were opened only after the study coordinator had confirmed a participant 's eligibility . Apart from the study coordinator , all research personnel , including the blood pressure technicians , and the study participants were unaware of treatment assignment . Study participants who were assigned to the intervention group received 40 g of isolated soybean protein supplement per day in cookies for 12 weeks , while those in the control group received 40 g of complex carbohydrate from wheat in cookies during the same period . The Sanjiang Food Company ( Heilongjiang province , People 's Republic of China ) provided the isolated soybean protein supplements . The soybean protein and control cookies were prepared central ly in Beijing and had the same appearance and taste . The daily nutritional content of the cookies was similar for those in the soybean protein supplement group and the control group , except for dietary protein and carbohydrate content : total energy ( 594.0 kcal vs. 577.1 kcal ) , protein ( 49.0 g vs. 12.9 g ) , carbohydrate ( 64.8 g vs. 95.3 g ) , fat ( 15.4 g vs. 16.1 g ) , saturated fat ( 2.4 g vs. 2.6 g ) , monounsaturated fat ( 6.2 g vs. 6.3 g ) , polyunsaturated fat ( 7.0 g vs. 7.2 g ) , and sodium ( 145.3 mg vs. 145.8 mg ) . The Food Science and Human Nutrition Laboratory of Iowa State University , Ames , Iowa , and Ralston Analytical Laboratories , St. Louis , Missouri , measured isoflavones in duplicate . The measurements were almost the same between the 2 laboratories , and we report the average . The daily portion of the soybean protein cookies contained 76.4 mg of total isoflavone , 44.9 mg of genistein , 26.5 mg of daidzein , and 4.9 mg of glycitein . During the intervention , a study dietitian instructed study participants to reduce other food intake so that the total energy intake would be constant during the course of the trial . Most study participants consumed study cookies in place of their usual breakfast , and a few study participants consumed study cookies in place of their usual lunch . Participants were also instructed to maintain their usual level of physical activity , alcohol intake , and dietary sodium intake . We monitored each participant 's body weight biweekly during the study and provided dietary consultation when we observed more than a 2-kg weight gain . The study participants returned unconsumed cookies at their 6- and 12-week follow-up visits after r and omization . The study coordinator counted the number of cookies returned , and we used this to assess the participants ' adherence to their assigned intervention . Measurements We collected information on demographic characteristics , medical history , medication use , alcohol consumption , and physical activity at baseline . Study staff members who were trained and certified in the use of Hawksley r and om-zero sphygmomanometers measured blood pressure . Blood pressure readings were taken from the right arm with appropriately sized cuffs after the participant had been seated quietly for 5 minutes . We obtained 3 blood pressure measurements at each of the 3 screening visits before intervention and at the follow-up visits at 6 and 12 weeks after r and omization . We measured weight , height , and waist circumference by using a st and ard protocol and calculated body mass index as kg/m2 . Experienced and trained research staff conducted a 24-hour dietary recall at the screening visit , the 6-week visit , and the 12-week visit . We calculated dietary nutrient intake on the basis of the China Food Composition Tables ( 18 ) . We obtained a 24-hour urinary specimen at the screening visit , the 6-week visit , and the 12-week visit to measure urinary excretion of sodium and potassium . Study staff assessed the presence of side effects ( 15 items ) by using a st and ard question naire at the 12-week follow-up visit . Statistical Analysis We design ed our trial to provide more than 80 % statistical power to detect a 3.0 mm Hg reduction in systolic blood pressure and a 2.0 mm Hg
Subgroup analyses showed smaller sample s reporting larger effect sizes ; intervention lasting less than 6 months showed larger effect sizes and intention-to-treat analysis showed smaller effect sizes Lifestyle interventions may be of value in preventing and reducing blood pressure in LMICs .
Despite the overwhelming evidence supporting the effectiveness of antihypertensive medication , hypertension remains poorly controlled in low and middle-income countries ( LMICs ) .