Effect of Soybean Protein on Blood Pressure: a Randomized, Controlled Trial

1
Effect of Soybean Protein on Blood Pressure a
Randomized, Controlled Trial

• Alicea Wei, MD
• UCSF FCM Journal Club
• October 12, 2005

2
Background

• Hypertension affects 50 million people in the
  U.S. and 1 billion people worldwide.1
• Hypertension is a modifiable risk factor for
  cardiovascular disease, stroke, and chronic
  kidney disease.
• Nutritional intervention, weight loss, exercise,
  and sodium restriction are important ways to
  prevent and treat hypertension.
• Effect of dietary macronutrients on BP has not
  been well-studied, although some trials encourage
  fruits, vegetables, low-saturated fat and low-fat
  dairy products to lower blood pressure.2

3
Why study dietary protein?

• Several studies have observed that dietary
  protein intake decreases BP.
• Burke et al.3 showed that protein supplementation
  reduced sBP and dBP by 5.9 mmHg (P 0.001) and
  2.6 mmHg (P 0.006) respectively.
• The sample size was 36.
• The duration of the study was 8 weeks.

4
Why study dietary protein?

• Another study gave conflicting results regarding
  dietary protein intake and BP effect.
• Washburn et al.4 showed that 20 g of protein per
  day does not produce statistically significant
  decrease in sBP or dBP, but when split into BID
  dosing, dBP decreased by 4.9 mmHg (P lt 0.05).
• The sample size was 51.
• The duration of the study was 6 weeks.

5
Why study dietary protein?

• Most of the studies had small sample sizes, short
  duration, and only a single BP measurement was
  obtained at baseline and then at termination of
  the studies.

6
Why study soy protein?

• 1/3 of FHC patients are Asian. 1/3 of FHC
  patients have hypertension. Because soy products
  remain an important aspect of Asian diet, it is
  important to understand the effect of their diet
  on their medical problems.
• There is a need for a randomized, double-blind,
  controlled multi-center trial to test the effect
  of soy protein on systolic and diastolic BP.

7
Methods

• The study was a randomized, double-blind, complex
  carbohydrate-controlled multi-center clinical
  trial.
• The study tested the effect of 40 g of isolated
  soy protein per day on systolic and diastolic BP
  in patients with prehypertension or stage 1
  hypertension.

8
Methods Study Participants

• The study participants were men and women 35-65
  years of age from three clinical centers in
  China Beijing, Xiulo, and Wuhan.
• Demographics, lifestyle, and dietary habits were
  similar in the three communities.
• The participants had initial sBP of 130-159 mmHg
  and dBP of 80-99 mmHg, or both. The readings
  were based on an average of 9 readings (3
  readings at 3 screening visits).

9
Methods Study Participants, Exclusion Criteria

• Use of anti-hypertensive in last 2 months
• H/o CV disease
• H/o diabetes mellitus
• H/o cancer
• H/o COPD
• H/o psychiatric disease

• H/o any serious illness that required additional
  medical treatment
• Cr gt 1.7
• EtOH gt 21 drinks/week
• pregnancy

10
Methods Study Participants

• Community BP prescreening recruited 862
  participants who met criteria and who were
  willing to participate in the study.
• Of those 862, 560 were excluded based on the
  preset exclusion criteria. The remaining 302
  participants entered the study.
• 150 were from Beijing, 84 were from Hebei, and 68
  were from Hubei.

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Methods Study Participant Characteristics
12
Methods Study Participants Flow Chart
13
Methods Intervention

• Computer-generated assignments allocated 150 to
  the soy protein supplementation group and 152 to
  the control group.
• Only the study coordinator knew treatment
  assignments.

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Methods Intervention

• Soy protein supplement group received 40g
  isolated soy protein cookies provided by Sanjiang
  Food Company.
• Control group received complex-carbohydrate
  cookies made in Beijing, which had the same look
  and taste as the soy cookies.
• Nutritional content of both cookies were similar,
  except for protein and carbohydrate content.

15
Methods Intervention
16
Methods Intervention

• A dietician instructed participants to decrease
  other food intake in order to have similar total
  energy intake duing the course of the trial.
• Most participants consumed the cookies in place
  of their usual breakfast. A few consumed in
  place of their usual lunch.
• Participants were instructed to maintain usual
  level of physical activity, EtOH intake, and
  dietary sodium intake.
• Dietary consultation was provided when
  participants gained gt2 kg in weight.

17
Methods Intervention

• Participant adherence was evaluated by returning
  of unconsumed cookies at 6-week and 12-week
  follow-up visits after randomization.

18
Methods Measurements

• BP measurements were taken from right arms after
  the subjects had been seated quietly for 5
  minutes.
• BP measurements were taken 3 times at 3 screening
  visits prior to the study, and at 6 weeks and 12
  weeks after randomization.
• 15-item side effects questionnaire given at the
  12-week study for assessment.

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Results

• 139 of 150 participants (92.7) from soy protein
  supplement group completed the study.
• 137 of 152 participants (90.1) from the control
  group completed the study.
• Soy protein group consumed 92.8 of their
  cookies.
• Control group consumed 92.6 of their cookies.
• Data represented are from 281 participants at 6
  weeks and 276 participants at 12 weeks.

20
Results sBP at 6 and 12 weeks
21
Results sBP at 6 weeks

• sBP was 5.9 mmHg (SD 11.2) in the control group
  and was 8.6 mmHg (SD 9.4) in the soy protein
  supplementation group.
• The net reduction in sBP was 2.66 mmHg (95 CI
  -0.21 to -5.11) for the soy protein group when
  compared with the control group.

22
Results sBP at 12 weeks

• sBP was 8.7 mmHg (SD 9.0) in the control group
  and was 13.0 in the soy protein supplementation
  group.
• The net reduction in sBP was 4.31 mmHg (95 CI
  -2.11 to -6.51) for the soy protein group when
  compared with the control group.

23
Results dBP at 6 and 12 weeks
24
Results dBP at 6 weeks

• dBP was 0.4 mmHg (SD 7.0) in the control group
  and was 1.6 mmHg (SD 6.8) in the soy protein
  supplementation group.
• The net reduction in dBP was 1.17 mmHg (95 CI
  0.46 to -2.80) for the soy protein group when
  compared with the control group.

25
Results dBP at 12 weeks

• dBP was 2.6 mmHg (SD 6.0) in the control group
  and was 5.4 mmHg (SD 5.8) in the soy protein
  supplementation group.
• The net reduction in dBP was 2.76 mmHg (95 CI
  was 1.35 to 4.16) for the soy protein group
  when compared with the control group.

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Results Subgroup Analysis
27
Results Subgroup Analysis

• Soy protein supplementation had similar effects
  in men vs. women, in age lt vs. ? 50 years, and
  not overweight vs. overweight.
• In normotensive (pre-hypertensive) vs.
  hypertensive subgroups, net reduction was greater
  in hypertensive participants than normotensive
  (pre-hypertensive) participants.
• Interaction between hypertensive status and BP
  effect was statistically significant for both sBP
  (P 0.01) and dBP (P 0.007).

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Results Side Effects

• Side effects were similar in both the control and
  soy protein supplementation groups.
• Self-reported side effects changes in appetite,
  nausea, stomach pain or burning, diarrhea,
  constipation, excessive gas, and skin rash
• No reports of bad taste in mouth, belching,
  polyuria, easy bruising, epistaxis, change in
  sexual drive, red stools, or black stools
• No changes in body weight in either group.

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Discussion

• This study had the largest sample size of 302
  participants, compared with Burke et al. and
  Washburn et al.
• This study had the longest duration of 12 weeks.
• This study recorded multiple BP readings at the
  beginning, at 6 weeks, and at 12 weeks of the
  trial.
• This study showed that soy protein
  supplementation decrease both sBP and dBP.

30
Discussion

• Even the complex carbohydrate (control) group
  demonstrated a decrease in BP over the 12 week
  trial period.
• Complex carbohydrates have been recommended to
  replace saturated fat in order to decrease CV
  risk.5
• This study showed that vegetable protein,
  specifically soy protein, may be an even better
  replacement for saturated fat, as it results in
  even greater reduction in sBP and dBP.

31
Discussion

• Because there was no significant differences in
  results within the different subgroups (men vs.
  women, age lt vs. ? 50 years, and not overweight
  vs. overweight), the results may be broadly
  applicable to the general population.
• This study showd soy protein supplementation
  decreases BP by 4.31/2.76 mmHg after 12 weeks of
  use. Wing et al.6 showed that diuretics decrease
  BP by 22/9 mmHg and ACE-Is decrease BP by 20/9
  mmHg after 1 year of use. Because the durations
  of the studies were different, it may be useful
  to conduct a study to evaluate the effect of
  long-term (1 year) soy supplementation on BP.
• Soy protein supplementation (for 12 weeks) may be
  useful for patients with borderline hypertension.

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Discussion Limitations of the Study

• The study was not designed to test for BP
  reduction effecting within the individual
  subgroups.
• The study was held exclusively in China. It is
  not clear whether soy protein supplementation has
  the same effects in the U.S. population or even
  Chinese immigrants to the U.S.
• A nutritionist was available during the trial to
  monitor total caloric intake. Reduced caloric
  intake from other foods may have biased the
  BP-lowering effect of soy protein.

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Discussion Limitations of the Study

• A nutritionist will not be available to closely
  monitor caloric intake and weight control in most
  cases.
• The soy protein cookies used in the study
  contained soy isoflavones genistein, daidzein,
  and glycitein. It is not known whether it is the
  soy protein itself or the metabolites that have
  the BP-lowering effect.

34
Discussion Drawbacks to Using Soy Protein?

• Few studies have shown that soy consumption is
  associated with increased risk for bladder CA.
• After adjusting for smoking and level of
  education, Sun et al. (2002)7 showed that the
  highest quartile of soy intake (gt 92.5 g/1000
  kCal) had 2.3-fold higher risk for bladder CA
  (95 CI 1.1-5.1) than the lowest quartile
  (lt36.9 g/1000 kCal) of energy-adjusted total soy
  protein intake in Asian populations.

35
Discussion Drawbacks to Using Soy Protein?

• Sun et al. (2004)8 reported relative risks of
  bladder CA are 2.05 for men consuming soy 1-2
  times per week, 2.45 for men consuming soy 3-6
  times per week, and 4.61 for men consuming soy
  daily (P 0.004 for trend). This is compared to
  men consuming soy lt once per week.

36
Discussion Possible Mechanisms

• The actual mechanism underlying the BP effect of
  soy protein is not known.
• Moncada and Higgs9 hypothesized that the high
  levels of arginine (precursor to nitric oxide) in
  soy protein causes vasodilation.
• Kuchel10 noted that protein intake leads to
  increased sodium, water, and urinary dopmine
  excretion, therefore causing a dopamine-mediated,
  protein-induced natriuresis to decrease BP.

37
Summary for Patients

• What is the problem?
• High BP is a common chronic problem in adults.
  It strains the heart and harms blood vessels. It
  increases risk for blindness, heart attack, heart
  failure, kidney problems, and stroke.
• What is known about it so far?
• In addition to using medicines, alternatives
  include dietary changes. Few small studies show
  that eating soybean protein could lower BP, but
  we dont know how significant it is.

38
Summary for Patients

• Why did the researchers do this new study?
• To see if soybean protein lowers systolic and
  diastolic blood pressure.
• Who was studied?
• 302 Chinese adults 35-64 years of age with
  high-normal or mildly elevated blood pressure.

39
Summary for Patients

• How was the study done?
• The researchers recruited people from 3 regions
  of China who had sBP of 130-159 mmHg or dBP of
  88-99 mmHg, or both. No one was on any medicines
  for their high BP. Half of the group was given
  40 g soybean protein cookies. Half of the group
  was given 40 g complex carbohydrates cookies.
  The researchers did not know who received which
  type of cookie. Participants ate the cookies in
  place of a meal for 12 weeks. Then their BPs
  were compared.

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Summary for Patients

• What did the researchers find?
• Soy cookies decreased both systolic and
  diastolic BP by about 3-4 mmHg more than complex
  carbohydrate cookies. A few side effects like
  appetite changes and stomach discomfort were
  reported.

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Summary for Patients

• What were the limitations of the study?
• The study was relatively short. We dont know
  if the results apply to people in the U.S. We
  dont know if its the soy protein itself or the
  soy protein metabolites in the cokies that
  decreased the blood pressure.
• What are the implications of the study?
• Soy protein supplementation may help lower
  blood pressure in some people.

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Discussion Question

• What would you tell your patients about this
  study?

43
References

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References

• 7 Sun CL, Yuan MJ, Arakawa K, Low SH, Lee HP, Yu
  MC. Dietary soy and increased risk of bladder
  cancer the Singapore Chinese Health Study.
  Cancer Epidemiol Biomarkers Prev.
  2002111674-1677.
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  MC. Dietary soy and increased risk of bladder
  cancer a prospective cohort study of men in
  Shanghai, China. Int J Cancer.
  2004112319-323.
• 9 Moncada S, Higgs A. The L-arginine-nitric
  oxide pathway. N Engl J Med. 19933292002-2012.
  
• 10 Kuchel O. Differential catecholamine
  responses to protein intake in healthy and
  hypertensive subjects. Am J Physiol.
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