The effect of a dietary portfolio compared to a DASH-type diet on blood pressure

Accepted Manuscript The Effect of a Dietary Portfolio Compared to a DASH-Type Diet on Blood Pressure D.J.A. Jenkins, P.J. Jones, J. Frohlich, B. Lamarche, C. Ireland, S.K. Nishi, K. Srichaikul, P. Galange, C. Pellini, D. Faulkner, R.J. de Souza, J.L. Sievenpiper, A. Mirrahimi, V.H. Jayalath, L.S. Augustin, B. Bashyam, L.A. Leiter, R. Josse, P. Couture, V. Ramprasath, C.W.C. Kendall PII:

S0939-4753(15)30010-7

DOI:

10.1016/j.numecd.2015.08.006

Reference:

NUMECD 1480

To appear in:

Nutrition, Metabolism and Cardiovascular Diseases

Received Date: 21 May 2015 Revised Date:

7 August 2015

Accepted Date: 12 August 2015

Please cite this article as: Jenkins D, Jones P, Frohlich J, Lamarche B, Ireland C, Nishi S, Srichaikul K, Galange P, Pellini C, Faulkner D, de Souza R, Sievenpiper J, Mirrahimi A, Jayalath V, Augustin L, Bashyam B, Leiter L, Josse R, Couture P, Ramprasath V, Kendall C, The Effect of a Dietary Portfolio Compared to a DASH-Type Diet on Blood Pressure, Nutrition, Metabolism and Cardiovascular Diseases (2015), doi: 10.1016/j.numecd.2015.08.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

The Effect of a Dietary Portfolio Compared to a DASH-Type Diet on Blood Pressure Running Title: JENKINS, Vegetable Protein, Blood Pressure, and CHD Risk

RI PT

Jenkins, DJA1-5, Jones, PJ6, Frohlich, J7, Lamarche, B8, Ireland, C1,4, Nishi, SK1,4, Srichaikul, K1,9, Galange, P1,9, Pellini, C1,9, Faulkner, D1,4, de Souza, RJ1,3,10, Sievenpiper, JL1,2,4, Mirrahimi, A1, Jayalath, VH1,4, Augustin, LS1, Bashyam, B1,4, Leiter, LA1-5, Josse, R2,3,5, Couture, P11, Ramprasath, V6, Kendall, CWC1,4,12 Clinical Nutrition & Risk Factor Modification Center; 2Division of Endocrinology and Metabolism, 3Li Ka Shing Knowledge Institute, St. Michael’s Hospital Toronto; 4Department of Nutritional Sciences, 5Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON; 6Richardson Center for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg; 7Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver; 8School of Nutrition, Institute of Nutrition and Functional Foods, Laval University, Quebec City; 9Faculty of Medicine, University of Ottawa, Ottawa, ON; 10Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON; 11Institute of Nutrition and Functional Foods, Laval University, Quebec City; 12College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK.

M AN U

SC

1

TE D

Address Correspondence to: David JA Jenkins Department of Nutritional Sciences, Faculty of Medicine University of Toronto Toronto, Ontario, CANADA M5S 3E2 Phone: (416) 867-7475 Fax: (416) 867-7492 Email: [email protected]

AC C

EP

Abstract Word Count: 245 Manuscript Word Count: 3150 Tables: 2 Figures: 1 Supplemental Tables: 4 Supplemental Figure: 1

Clinical Trial Reg. No.: NCT00438425, clinicaltrials.gov

ACCEPTED MANUSCRIPT

ABSTRACT Background and Aim: Compared to a DASH-type diet, an intensively applied dietary portfolio

RI PT

reduced diastolic blood pressure at 24 weeks as a secondary outcome in a previous study. Due to the importance of strategies to reduce blood pressure, we performed an exploratory analysis pooling data from intensively and routinely applied portfolio treatments from the same study to assess the effect over time on systolic, diastolic and mean arterial pressure (MAP), and the

SC

relation to sodium (Na+), potassium (K+), and portfolio components.

Methods and Results: 241 participants with hyperlipidemia, from four academic centers across

M AN U

Canada were randomized and completed either a DASH-type diet (control n=82) or a dietary portfolio that included, soy protein, viscous fibers and nuts (n=159) for 24 weeks. Fasting measures and 7-day food records were obtained at weeks 0, 12 and 24, with twenty-four-hour urines at weeks 0 and 24. The dietary portfolio reduced systolic, diastolic and mean arterial

TE D

blood pressure compared to the control by 2.1mmHg (95% CI, 4.2 to -0.1mmHg) (p=0.056), 1.8mmHg (CI, 3.2 to 0.4mmHg) (p=0.013) and 1.9mmHg (CI, 3.4 to 0.4mmHg) (p=0.015), respectively. Blood pressure reductions were small at 12 weeks and only reached significance at

EP

24 weeks. Nuts, soy and viscous fiber all related negatively to change in mean arterial pressure (ρ=-0.15 to -0.17, p≤0.016) as did urinary potassium (ρ=-0.25, p=0.001), while the Na+/K+ ratio

AC C

was positively associated (ρ=0.20, p=0.010). Conclusions: Consumption of a cholesterol-lowering dietary portfolio also decreased blood pressure by comparison with a healthy DASH-type diet.

Key Words: vegetable protein; plant protein; sodium; blood pressure; coronary heart disease risk; cardiovascular disease.

1

ACCEPTED MANUSCRIPT

Abbreviations: Apo-A1 (apolipoprotein A1), Apo-B (apolipoprotein B), BMI (body mass index), CHD (coronary heart disease), CHO (carbohydrate), CI (confidence interval), CRP (Creactive protein), CVD (cardiovascular disease), DASH (Dietary Approaches to Stop

RI PT

Hypertension), DBP (diastolic blood pressure), FRS (Framingham Risk Score), HDL-C (highdensity lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol), MUFA (monounsaturated fatty acids), PUFA (polyunsaturated fatty acids), SBP (systolic blood

SC

pressure), SFA (saturated fatty acids), TC:HDL (total cholesterol:high-density lipoprotein

AC C

EP

TE D

M AN U

cholesterol), TG (triglycerides), waist (waist circumference)

2

ACCEPTED MANUSCRIPT

INTRODUCTION The DASH (Dietary Approaches to Stop Hypertension)1 and OmniHeart2 diets have reignited3 interest in using diet as the treatment for elevated blood pressure and have been the

RI PT

dietary approach of choice for both hypertension and cardiovascular disease risk reduction4. The dietary portfolio has also been recommended for cardiovascular risk reduction5-7. We have therefore undertaken an exploratory analysis of a previously published dietary portfolio

SC

study that focused on blood lipid changes and demonstrated a 13-14% reduction in LDL-C8. That study also demonstrated a significant reduction in diastolic blood pressure on the intensive

M AN U

portfolio arm as a secondary outcome when compared to a DASH-type diet. The dietary portfolio promotes consumption of nuts, soy protein, plant sterols, and viscous fiber to lower serum cholesterol, but of these dietary components nuts, soy protein, and viscous fiber may also lower blood pressure9-11. In the present analysis we combined the intensively and less

TE D

intensively applied dietary portfolio treatments to strengthen the power of the study. The data for these two treatments were combined since no significant differences were seen in changes in blood pressure, lipids or dietary compliance with key ingredients. We have added the 12 week

EP

data to allow the effect over time to be assessed and also added urinary measures of sodium and potassium, as indicators of dietary intake that may influence blood pressure. This diet was

AC C

compared with the healthy DASH-type diet as a positive control.

METHODS

This is a secondary analysis of a study with methods that have been reported previously

in detail8. The study complies with the Declaration of Helsinki, and was approved by the ethics committees of St. Michael’s Hospital and the Universities of Laval, Toronto, Manitoba, British

3

ACCEPTED MANUSCRIPT

Columbia and the Natural Health Products Directorate at Health Canada. Participant written informed consent was obtained prior to starting the study. Participants

RI PT

241 participants with hyperlipidemia (93 men and 148 postmenopausal women), >20 to 85 years, were recruited from 4 centres across Canada. They completed both the original study and provided 7-day diet histories at the start and end of the study period (Supplemental Figure Those with a history of cancer or a strong family history of cancer, cardiovascular disease,

SC

1)8.

untreated hypertension (blood pressure 140/90 mmHg or greater), diabetes, renal or liver disease,

M AN U

currently on lipid lowering medications, or smokers were excluded. Study Protocol

In brief, a randomized controlled parallel trial was conducted, involving 3 diets; intensive portfolio (monthly visits), routine portfolio and control (one 3 month visit for both), each for a

TE D

duration of 24 weeks. Blood pressure was measured at each visit 3 times and the average recorded, using a digital blood pressure monitor (Omron HEM-907XL, Omron Healthcare Inc, Vernon Hills, Illinois). Twenty-four hour urine collections were made at 3 sites at the start and

Diets

EP

end of each treatment (n=164).

AC C

Participants were counseled at each visit by dietitians to follow weight maintaining

vegetarian diets during the 6 month study period. Each participant was given a 7 day study food checklist to follow8. For both the intensive and routine dietary portfolio the recommended targets were: 9.8g of viscous fibers per 1000 kcal diet, from barley, oats, psyllium, eggplant, and okra; 22.5 g of soy protein per 1000 kcal, from components of soy milk, tofu and soy meat analogues; 22.5 g of nuts per 1000 kcal; and 0.94 g of plant sterols per 1000 kcal from a margarine enriched

4

ACCEPTED MANUSCRIPT

with plant sterol esters.8 The control dietary intervention emphasized avoidance of the specified core portfolio dietary components above and recommended a lacto-ovo-vegetarian DASH-type

vegetables, and a reduction in red meat and snack foods.12

RI PT

diet that focused on low saturated fat, whole grain cereals with low fat dairy, fruit and

Adherence with the dietary interventions was estimated as mean daily intakes from 7-day diet histories. For the dietary portfolio adherence was assessed based on servings of soy protein

SC

foods, nuts, viscous fiber foods, and plant sterol margarine consumed, with each contributing 25% when taken at the recommended amount (Supplemental Table 1a). For the DASH-type

M AN U

diet, increased servings of fruit, vegetables and low fat dairy contributed positively to the score and servings of red meat and snack foods consumed contributed negatively to the score. The number of servings, expressed as a percentage (one serving = 7.75%) were used to assess adherence based on the average DASH servings of fruit, vegetables and low fat dairy, providing

TE D

a total of 12.9 servings per 2000kcal diet (100% adherence) as recommended in a recent publication (Supplemental Table 1b)12. Analyses

EP

Blood samples were analyzed in each centre’s hospital or routine laboratory, and diets were analyzed using a program based on the US Department of Agriculture data8.

AC C

Statistical Analysis

The results are expressed as means [95% confidence interval (CI)]. No significant

differences were observed in the original report between the intensive and routine treatments in terms of dietary compliance, or changes in body weight, blood lipids or blood pressure.8 Therefore the two dietary portfolios were considered here as a single treatment with 241 participants completing the study. The primary outcome was change in mean arterial pressure

5

ACCEPTED MANUSCRIPT

from baseline to week 24 in the completers. This measure combines systolic and diastolic blood pressure in the ratio 1 SBP: 2 DBP. A repeated measures mixed-effects model, using compound symmetry covariance (PROC MIXED, SAS version 9.4), was used to estimate least squares

RI PT

mean within and between-treatment changes for all variables. The results are presented both with and without adjustment for changes in covariates such as waist, BMI, age, sex, blood pressure medication and baseline values. C-reactive protein (CRP) values were log transformed to satisfy

SC

distributional assumptions. A sensitivity analysis was conducted using generalized estimating equations (PROC GENMOD) with an exchangeable correlation structure is used to validate the

M AN U

findings obtained from mixed-effect model. The MIXED models were also run excluding participants on blood pressure medications, as well as using all participants providing at least one post-randomization measure (intention-to-treat).

Complete dietary data was only available for week 0 and week 24. Change in dietary

TE D

variables was expressed as percent kilocalories for macronutrients and milligrams/1000 kilocalories for micronutrients. Both baseline and change values of the three active dietary components assessed were found to be non-normally distributed (Shapiro-Wilk p<0.005), and a

EP

large number of participants were consuming none of the components at baseline (nuts n=39, soy protein foods n=128, viscous fiber foods n=34). Therefore, Spearman correlations (PROC

AC C

CORR) were used to assess the relation between the dietary intakes data and changes in blood pressure using the data from all the treatments. Urinary data were treated similarly. The Framingham coronary heart disease and cardiovascular risk factor scores (FRS) were

calculated using the variables of age, sex, systolic blood pressure, total cholesterol and HDL-C, the exclusion criteria accounted for diabetes and smoking status13 .

RESULTS

6

ACCEPTED MANUSCRIPT

Dietary adherence, in terms of desired number of servings, was 48% on the dietary portfolio and 105% on the DASH-type control (Supplemental Table 1a-b) at week 24. A relative increase in fat intake was observed on the portfolio compared to the control by 8% of total

RI PT

calories with a corresponding reduction in available carbohydrate (p<0.0001), and related to increased nut intake. No change was seen in total protein intake, but a 30% (95% CI, 26 to 34%) (p<0.0001) relative increase in vegetable protein as a proportion of total protein was observed in

SC

the portfolio group. Sodium intake remained constant but potassium was significantly higher on the control diet by 127mg/d (CI, -242 to -12mg/d) (p=0.031). No difference was seen between

M AN U

the portfolio and control treatments in the change in body weight, BMI, or waist circumference (Table 1). Blood Pressure

There was no significant difference in the number of people taking blood pressure medications

TE D

by treatment (Fisher’s exact test, p=0.235). In the portfolio and control diet groups, 28 (18%) and 20 (24%) participants, respectively, were taking blood pressure medications. No changes were observed in use of blood pressure medications throughout the study. Using completer data from

EP

12 and 24 weeks in the unadjusted model for the primary analysis; systolic, diastolic, and mean arterial pressure were reduced on the portfolio diet by 2.5mmHg(CI, 3.7 to 1.2mmHg) (p<0.001),

AC C

2.0mmHg(CI, 2.8 to 1.2mmHg) (p<0.001), and 2.1mmHg(CI, 3.0 to 1.3mmHg) (p<0.001), respectively, with no significant changes on the control diet, resulting in relative reductions in blood pressure on the portfolio: for systolic 2.1mmHg(CI, 4.2 to -0.1mmHg) (p=0.056); diastolic of 1.8mmHg(CI, 3.2 to 0.4mmHg) (p=0.013); and mean arterial pressure of 1.9mmHg(CI, 3.4 to 0.4mmHg) (p=0.015) (Table 1). A sensitivity analysis using generalized estimating equations for

7

ACCEPTED MANUSCRIPT

the reduction in systolic blood pressure values were significant at 2.1mmHg (CI, 4.1 to 0.1mmHg) (p=0.040). After including baseline, waist circumference, BMI, age, sex, and blood pressure

relative reductions were maintained (Table 1).

RI PT

medication as covariates in the repeated measures (weeks 12 and 24) model, the significance of

Using all available data from the original study participants (n=345) showed similar

SC

treatment differences and significance levels to those reported for the completer data. The fully adjusted model showed reductions in systolic blood pressure, 1.8mmHg (CI, 3.7 to -0.05) p =

M AN U

0.057, diastolic blood pressure, 1.3mmHg (CI,2.4 to 0.1) p = 0.033, and mean arterial pressure 1.5mmHg (CI, 2.7 to 0.2) p = 0.022). Similarly, elimination of those on blood pressure medications also confirmed these treatment differences in blood pressure (reductions in systolic blood pressure, 2.6mmHg, (CI, 4.7 to 0.5) p = 0.009, diastolic blood pressure, 1.5mmHg, (CI,

TE D

2.9 to 0.2) p = 0.027, mean arterial pressure 1.9mmHg (CI, 3.3 to0.5) p = 0.009). Framingham Cardiovascular Risk Score

A corresponding relative reduction was seen on the portfolio in 10-year cardiovascular

EP

risk scores for both coronary heart disease and cardiovascular disease 1.2%(CI, 1.7 to 0.7%, p<0.001) and 1.4% (CI, 2.0 to 0.8%, p<0.001) respectively. This risk reduction was in turn

AC C

contributed to by the relative reduction in total cholesterol of 0.7mmol/L (CI, 0.9 to 0.5mmol/L) (p<0.001) on the portfolio with no change in HDL-C. There were also corresponding reductions in both apolipoprotein-B [0.2g/L(CI, 0.2 to 0.1g/L), p<0.001] and log CRP concentrations [0.3mg/L(CI, 0.4 to 0.1mg/L), log CRP p=0.007] (Table 1). The servings of dietary portfolio foods were also related to reductions in CHD and CVD risk (Table 2). Key Components of the Dietary Portfolio compared to DASH-type Control

8

ACCEPTED MANUSCRIPT

On the dietary portfolio treatment differences included relative increases in intake of nuts [17g/1000kcal/d(CI, 15 to 20g/1000 kcal/d)], soy protein [3.4%(CI, 2.8 to 3.9%) of total calories

compared to the control group (Supplemental Table 3).

RI PT

equivalent to 13.6 g/1000 kcal/d], and viscous fibers [4.6g/1000kcal(CI, 3.8 to 5.3g/1000 kcal)]

Using spearman correlations, and pooling test and control treatments, change in dietary portfolio adherence was related significantly to change in diastolic (ρ=-0.18, p=0.006) and mean

SC

arterial pressure (ρ=-0.16, p=0.011). No significant associations were seen with DASH

adherence. Change in all three key dietary portfolio components were also significantly related to

M AN U

reductions in mean arterial pressure: nuts (ρ=-0.15, p=0.016), soy (ρ=-0.16, p=0.015), and viscous fiber (ρ=-0.17, p=0.009), similar associations were seen for systolic and diastolic blood pressures. (Table 2) Among participants on the DASH-type control diet, no significant correlations were seen between portfolio adherence and blood pressure outcomes; however,

TE D

DASH adherence showed significant negative correlations with systolic (ρ=-0.35, P=0.001), diastolic (ρ=-0.24, P=0.033) and mean arterial pressure (ρ=-0.30, P=0.005). No associations were seen between adherence to either diet and blood pressure amongst participants on the

EP

dietary portfolio diet (Supplemental Table 4). Dietary Na+, K+, and Na+/K+ Ratio

AC C

Treatment differences included a relative reduction in dietary potassium on the portfolio

due to an absolute increase in dietary potassium intake on the control diet [127mg/1000kcals (CI, -242 to -12mg/1000 kcals), p=0.031] with no changes in dietary sodium. Further there was no association between the change in dietary potassium, sodium, or the sodium to potassium ratio with any blood pressure measure. However baseline dietary potassium and the Na+/K+ ratios, but not sodium, were significantly related to baseline mean arterial pressure (ρ=-0.19, n=241,

9

ACCEPTED MANUSCRIPT

p=0.004, and ρ=0.19, n=241, p=0.004; and ρ=0.08, n=241, p=0.195) respectively. Similar associations were seen for systolic and diastolic blood pressure. Urine Na+ and K+: Relation to Diet and Blood Pressure

RI PT

Creatinine adjusted urinary potassium output increased on the DASH-type control

relative to the portfolio [0.9 (CI 1.6 to 0.2) p = 0.016] in keeping with the dietary increase.

(Supplementary Table 3) As anticipated urinary measures were significantly correlated with

SC

dietary measures: sodium (baseline ρ=0.29, p<0.001), potassium (baseline ρ=0.42, week 24 ρ=0.45, and change ρ=0.33, all p<0.001), as well as dietary protein intake compared to urinary

M AN U

urea output (baseline ρ=0.27, p<0.001, and change ρ=0.17 p= 0.028).

However unlike the dietary measures, urinary changes in potassium correlated inversely with changes in systolic (ρ=-0.25, p=0.001), diastolic (ρ=-0.23, p=0.004), and mean arterial pressure (ρ=-0.25, p=0.001); while the Na+/K+ ratio related positively to changes in: systolic

TE D

(ρ=0.21, p=0.007), diastolic (ρ=0.17, p=0.026), and mean arterial pressure (ρ=0.20, p=0.010). Changes in urinary sodium did not relate to changes in blood pressure, possibly due to the lack of

EP

significant change in dietary sodium intake and urinary sodium output.

DISCUSSION

This exploratory analysis indicated that consumption of the dietary portfolio lowers blood

AC C

pressure when compared with a healthy DASH-type diet emphasizing low fat dairy, fruit and vegetables, whole grains, reduced meat intake and elimination of snack foods. The modest effect at 2 mmHg was therefore in addition to what would be expected from DASH-type diets that have produced 10 mmHg blood pressure reductions in study participants with an initial mean systolic blood pressure of 130 mmHg12. This blood pressure reduction, combined with the effect of the dietary portfolio in the blood lipid profile, resulted in a significant reduction in the

10

ACCEPTED MANUSCRIPT

cardiovascular disease risk score. Despite excellent compliance of over 100%, the DASH-type diet nevertheless failed to reduce blood pressure probably because the baseline therapeutic diet of the participants already had many of the DASH diet features (already over 60% compliance)

RI PT

and blood pressure was already low at 119/73 mmHg. Nevertheless increased compliance to the DASH diet components on the control was still associated with reduced blood pressure.

For cardiovascular risk reduction, the Canadian Cardiovascular Society has promoted use

SC

of the DASH and Mediterranean diets, as well as the dietary portfolio, also recommended for statin intolerance by the European Atherosclerosis Society, based on its cholesterol lowering

M AN U

potential; and the American Heart Association/American College of Cardiology guidelines recommend the DASH diet6, 7, 14. The present study demonstrates a blood pressure advantage of increasing vegetable fat and protein, in keeping with blood pressure and cardiovascular advantages from other studies12, 15.

TE D

Consumption of 30 g of mixed nuts (walnuts, almonds and hazelnuts) as part of a Mediterranean diet (50% diabetes) was associated with a significant 0.65 mmHg reduction in diastolic blood pressure possibly related to the monounsaturated fat content16. The mean nut

EP

intake in the present study was ~36 g/d. Similarly soy protein has been shown in a number of studies and through a meta-analysis to lower blood pressure10, 17. Viscous fiber intake has also

AC C

been associated with blood pressure reduction18. Soluble fiber from fruit and vegetable intake reduced coronary heart disease risk19, with strong data for cereal fiber that in some but not all studies reduced cardiovascular risk factors20. There is uncertainty over the ideal level of salt reduction1, 21-26. Our data pose the

question of whether foods that have both blood pressure and lipid lowering properties could be permitted to contain more salt to improve palatability than less cardiovascular protective foods.

11

ACCEPTED MANUSCRIPT

Thus, the present dietary portfolio that reduced systolic blood pressure by 2.5 mmHg across the dietary period, also reduced total-cholesterol:HDL-C by 10-11% providing a reduction in FRS of 1.6% per 10 years. Addition of an extra 500 mg of sodium to that diet would be predicted to

RI PT

increase systolic blood pressure by only 1.22 mmHg1 but would lessen the reduction in the FRS by only 0.2% still leaving a benefit of 1.4% reduced risk per 10 years.

The study weakness includes the fact that blood pressure was not the primary outcome;

SC

the present analysis was therefore a secondary, exploratory analysis with all the limitations that post hoc analyses involve. 24-hour ambulatory blood pressure may have provided a better

M AN U

reflection of the effect of the dietary interventions27. In addition baseline blood pressure was low at 119/73 mmHg making further reductions difficult and thus likely underestimating the true blood pressure lowering effect1. Good adherence to a DASH-type diet at baseline (65-68%) further limited demonstration of blood pressure lowering of both portfolio and DASH-type

TE D

control treatments and illustrated the ease of compliance with the DASH diet. The dietary portfolio was only complied with by 48%, which limits the effect that could potentially be expected. Nevertheless, 14% LDL-C reduction was still observed at this compliance level8

EP

compared to the 30% LDL-C reduction seen when all portfolio foods were provided under metabolic conditions28. The colinearity of the active ingredients by the design of the diets made it

AC C

difficult to undertake multiple regression. The sodium effect could have been explored with two levels of sodium intake as was demonstrated in the DASH diet1. The strength of the study was the demonstration in centres across the continent that

healthy food components may create diets that address many risks factors, including blood pressure, blood lipids, and inflammatory biomarkers as part of a broad based cardiovascular disease risk reduction strategy.

12

ACCEPTED MANUSCRIPT

We conclude that a dietary portfolio emphasizing cholesterol lowering foods also reduces blood pressure. Overall, plant based diets, notably the PREDIMED diet, emphasizing foods higher in protein, oil, and fiber have been associated with reduced cardiovascular disease and

RI PT

stroke15, 29. A recent meta-analysis of vegetarian diets also demonstrated a reduction in blood pressure30 further supporting the use of plant foods for the reduction of blood pressure. Future studies could usefully compare the effects of the dietary portfolio with the DASH diet in

FUNDING

SC

moderately hypertensive participants with blood pressure as the primary outcome.

M AN U

This work was supported by the CRCE of the Federal Government of Canada (Drs Jenkins, Jones, and Lamarche), Canadian Institutes for Health Research, Advanced Foods & Materials Canada Net, Loblaw Brands Ltd, Solae (St. Louis, Missouri), and Unilever (Vlaardingen, the Netherlands, and Toronto, Ontario, Canada). Unilever Research and

TE D

Development provided the donation of margarines used in the study and Can-Oat Milling, a division of Viterra Inc (Portage la Prairie, Manitoba, Canada), provided the generous donation of HiFi medium oat bran used for the study breads and funding for freezer acquisition. St.

EP

Michael’s Hospital Foundation provided funding for the production of the study booklet. Funding organizations and sponsors played no role in the design and conduct of the study; the

AC C

collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript.

13

ACCEPTED MANUSCRIPT

CONFLICTS OF INTEREST D.J.A.J. has received research grants from Saskatchewan Pulse Growers, the Agricultural Bioproducts Innovation Program through the Pulse Research Network, the Advanced Foods and

RI PT

Material Network, Loblaw Companies Ltd., Unilever, Barilla, the Almond Board of California, Agriculture and Agri-food Canada, Pulse Canada, Kellogg's Company, Canada, Quaker Oats, Canada, Procter & Gamble Technical Centre Ltd., Bayer Consumer Care, Springfield, NJ,

SC

Pepsi/Quaker, International Nut & Dried Fruit (INC), Soy Foods Association of North America, the Coca-Cola Company (investigator initiated, unrestricted grant), Solae, Haine Celestial, the

M AN U

Sanitarium Company, Orafti, the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, the Canola and Flax Councils of Canada, the CCC, the CIHR, the Canada Foundation for Innovation and the Ontario Research Fund. He has been on the speaker's panel, served on the scientific advisory board and/or received travel support and/or

TE D

honoraria from the Almond Board of California, Canadian Agriculture Policy Institute, Loblaw Companies Ltd, the Griffin Hospital (for the development of the NuVal scoring system, the Coca-Cola Company, EPICURE, Danone, Saskatchewan Pulse Growers, Sanitarium Company,

EP

Orafti, the Almond Board of California, the American Peanut Council, the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Herbalife

AC C

International, Pacific Health Laboratories, Nutritional Fundamental for Health, Barilla, Metagenics, Bayer Consumer Care, Unilever Canada and Netherlands, Solae, Kellogg, Quaker Oats, Procter & Gamble, the Coca-Cola Company, the Griffin Hospital, Abbott Laboratories, the Canola Council of Canada, Dean Foods, the California Strawberry Commission, Haine Celestial, PepsiCo, the Alpro Foundation, Pioneer Hi-Bred International, DuPont Nutrition and Health, Spherix Consulting and WhiteWave Foods, the Advanced Foods and Material Network, the

14

ACCEPTED MANUSCRIPT

Canola and Flax Councils of Canada, the Nutritional Fundamentals for Health, Agri-Culture and Agri-Food Canada, the Canadian Agri-Food Policy Institute, Pulse Canada, the Saskatchewan Pulse Growers, the Soy Foods Association of North America, the Nutrition Foundation of Italy

RI PT

(NFI), Nutra-Source Diagnostics, the McDougall Program, the Toronto Knowledge Translation Group (St. Michael's Hospital), the Canadian College of Naturopathic Medicine, The Hospital for Sick Children, the Canadian Nutrition Society (CNS), the American Society of Nutrition

SC

(ASN), Arizona State University, Paolo Sorbini Foundation and the Institute of Nutrition,

Metabolism and Diabetes. He received an honorarium from the US Department of Agriculture to

M AN U

present the 2013 W.O. Atwater Memorial Lecture. He received the 2013 Award for Excellence in Research from the International Nut and Dried Fruit Council. He received funding and travel support from the Canadian Society of Endocrinology and Metabolism to produce mini cases for the CDA. He is a member of the ICQC. D.J.A.J’s wife is a director and partner of Glycemic

TE D

Index Laboratories, Toronto, Ontario, Canada, and his sister received funding through a grant from the St. Michael's Hospital Foundation to develop a cookbook for one of his studies. C.W.C.K. has received honoraria from the Almond Board of California, the International Tree

EP

Nut Council Nutrition Research & Education Foundation, Barilla, and Unilever Canada. C.W.C.K. has been on the speaker’s panel for the Almond Board of California; and has received

AC C

research grants from Loblaws, Unilever, Barilla, and the Almond Board of California. B.L. and P.C, have received research grants from the Dairy Farmers of Canada, Dairy Australia. B.L. has received research funding from the Danone Institute and Atrium Innovations and honoraria from Unilever, Danone, and the Dairy Farmers of Canada. B.L. is Chair in Nutrition and Cardiovascular Health, supported in part by Provigo/Loblaws. S.K.N. has received research support from the Canadian Institutes of Health Research (CIHR), Ontario Graduate Scholarship

15

ACCEPTED MANUSCRIPT

(OGS), and the Canadian Foundation for Dietetic Research for work on clinical trials assessing the effect of nut intake on health outcomes. S.K.N. is also a clinical research dietitian at Glycemic Index Laboratories, Inc. R.S. is funded by a CIHR Postdoctoral Fellowship Award

RI PT

and has received research support from the CIHR, the Calorie Control Council, the Canadian Foundation for Dietetic Research and the Coca-Cola Company (investigator initiated,

unrestricted grant). R.S. has served as an external resource person to WHO’s Nutrition

SC

Guidelines Advisory Group and received travel support from WHO to attend group meetings. J.L.S. has received research support from the Calorie Control Council, the Coca-Cola Company

M AN U

(investigator initiated, unrestricted grant), Pulse Canada, and the International Tree Nut Council Nutrition Research and Education Foundation. J.L.S. has received travel funding, speaker fees or honoraria from the American Heart Association, the American Society for Nutrition, the National Institute of Diabetes and Digestive and Kidney Diseases, the Canadian Diabetes

TE D

Association, the Canadian Nutrition Society, the Calorie Control Council, the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes, the International Life Sciences Institute North America, the International Life Sciences Institute Brazil, the

EP

University of South Carolina, the University of Alabama at Birmingham, the Canadian Sugar Institute, Oldways Preservation Trust, the Nutrition Foundation of Italy, Abbott Laboratories,

AC C

Pulse Canada, Dr. Pepper Snapple Group and the Coca-Cola Company. J.L.S. is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of both the Canadian Diabetes Association and the European Association for the Study of Diabetes, and he is on the American Society for Nutrition writing panel for a scientific statement on the metabolic and nutritional effects of fructose, sucrose and high-fructose corn syrup. J.L.S. is a member of the Carbohydrate Quality Consortium and an unpaid scientific advisor for the Food, Nutrition and Safety Program

16

ACCEPTED MANUSCRIPT

of the International Life Science Institute North America. His wife is an employee of Unilever Canada. No competing interests were declared by CI, KS, PG, CP, DF, AM, VHJ, LSA, BB, RJ,

AC C

EP

TE D

M AN U

SC

RI PT

PC, VR, JF, and LL.

17

ACCEPTED MANUSCRIPT

REFERENCES

AC C

EP

TE D

M AN U

SC

RI PT

1. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, Obarzanek E, Conlin PR, Miller ER, 3rd, Simons-Morton DG, Karanja N, Lin PH and Group DA-SCR. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344:3-10. 2. Appel LJ, Sacks FM, Carey VJ, Obarzanek E, Swain JF, Miller ER, 3rd, Conlin PR, Erlinger TP, Rosner BA, Laranjo NM, Charleston J, McCarron P and Bishop LM. Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. Jama. 2005;294:2455-64. 3. Kempner W. Treatment of heart and kidney disease and of hypertensive and arteriosclerotic vascular disease with the rice diet. Ann Intern Med. 1949;31:821-56, illust. 4. Go AS, Bauman MA, Coleman King SM, Fonarow GC, Lawrence W, Williams KA and Sanchez E. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Journal of the American College of Cardiology. 2014;63:1230-8. 5. Grundy SM, Cleeman JI, Merz CN, Brewer HB, Jr., Clark LT, Hunninghake DB, Pasternak RC, Smith SC, Jr. and Stone NJ. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Journal of the American College of Cardiology. 2004;44:720-32. 6. Anderson TJ, Gregoire J, Hegele RA, Couture P, Mancini GB, McPherson R, Francis GA, Poirier P, Lau DC, Grover S, Genest J, Jr., Carpentier AC, Dufour R, Gupta M, Ward R, Leiter LA, Lonn E, Ng DS, Pearson GJ, Yates GM, Stone JA and Ur E. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. The Canadian journal of cardiology. 2013;29:151-67. 7. Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, Roden M, Stein E, Tokgozoglu L, Nordestgaard BG, Bruckert E, De Backer G, Krauss RM, Laufs U, Santos RD, Hegele RA, Hovingh GK, Leiter LA, Mach F, Marz W, Newman CB, Wiklund O, Jacobson TA, Catapano AL, Chapman MJ and Ginsberg HN. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. European heart journal. 2015. 8. Jenkins DJ, Jones PJ, Lamarche B, Kendall CW, Faulkner D, Cermakova L, Gigleux I, Ramprasath V, de Souza R, Ireland C, Patel D, Srichaikul K, Abdulnour S, Bashyam B, Collier C, Hoshizaki S, Josse RG, Leiter LA, Connelly PW and Frohlich J. Effect of a dietary portfolio of cholesterol-lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia: a randomized controlled trial. JAMA. 2011;306:831-9. 9. Sabate J, Fraser GE, Burke K, Knutsen SF, Bennett H and Lindsted KD. Effects of walnuts on serum lipid levels and blood pressure in normal men. N Engl J Med. 1993;328:603-7. 10. Dong JY, Tong X, Wu ZW, Xun PC, He K and Qin LQ. Effect of soya protein on blood pressure: a meta-analysis of randomised controlled trials. The British journal of nutrition. 2011;106:317-26. 11. Streppel MT, Arends LR, van 't Veer P, Grobbee DE and Geleijnse JM. Dietary fiber and blood pressure: a meta-analysis of randomized placebo-controlled trials. Archives of internal medicine. 2005;165:150-6.

18

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

12. Sacks FM, Carey VJ, Anderson CA, Miller ER, 3rd, Copeland T, Charleston J, Harshfield BJ, Laranjo N, McCarron P, Swain J, White K, Yee K and Appel LJ. Effects of high vs low glycemic index of dietary carbohydrate on cardiovascular disease risk factors and insulin sensitivity: the OmniCarb randomized clinical trial. Jama. 2014;312:2531-41. 13. D'Agostino RB, Sr., Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM and Kannel WB. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117:743-53. 14. Eckel RH, Jakicic JM, Ard JD, de Jesus JM, Houston Miller N, Hubbard VS, Lee IM, Lichtenstein AH, Loria CM, Millen BE, Nonas CA, Sacks FM, Smith SC, Jr., Svetkey LP, Wadden TA, Yanovski SZ, Kendall KA, Morgan LC, Trisolini MG, Velasco G, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC, Jr. and Tomaselli GF. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S76-99. 15. Halton TL, Willett WC, Liu S, Manson JE, Albert CM, Rexrode K and Hu FB. Lowcarbohydrate-diet score and the risk of coronary heart disease in women. N Engl J Med. 2006;355:1991-2002. 16. Toledo E, Hu FB, Estruch R, Buil-Cosiales P, Corella D, Salas-Salvado J, Covas MI, Aros F, Gomez-Gracia E, Fiol M, Lapetra J, Serra-Majem L, Pinto X, Lamuela-Raventos RM, Saez G, Bullo M, Ruiz-Gutierrez V, Ros E, Sorli JV and Martinez-Gonzalez MA. Effect of the Mediterranean diet on blood pressure in the PREDIMED trial: results from a randomized controlled trial. BMC medicine. 2013;11:207. 17. Jenkins DJ, Kendall CW, Jackson CJ, Connelly PW, Parker T, Faulkner D, Vidgen E, Cunnane SC, Leiter LA and Josse RG. Effects of high- and low-isoflavone soyfoods on blood lipids, oxidized LDL, homocysteine, and blood pressure in hyperlipidemic men and women. Am J Clin Nutr. 2002;76:365-72. 18. Vuksan V, Jenkins DJ, Spadafora P, Sievenpiper JL, Owen R, Vidgen E, Brighenti F, Josse R, Leiter LA and Bruce-Thompson C. Konjac-mannan (glucomannan) improves glycemia and other associated risk factors for coronary heart disease in type 2 diabetes. A randomized controlled metabolic trial. Diabetes care. 1999;22:913-9. 19. Pereira MA, O'Reilly E, Augustsson K, Fraser GE, Goldbourt U, Heitmann BL, Hallmans G, Knekt P, Liu S, Pietinen P, Spiegelman D, Stevens J, Virtamo J, Willett WC and Ascherio A. Dietary fiber and risk of coronary heart disease: a pooled analysis of cohort studies. Archives of internal medicine. 2004;164:370-6. 20. Giacco R, Clemente G, Cipriano D, Luongo D, Viscovo D, Patti L, Di Marino L, Giacco A, Naviglio D, Bianchi MA, Ciati R, Brighenti F, Rivellese AA and Riccardi G. Effects of the regular consumption of wholemeal wheat foods on cardiovascular risk factors in healthy people. Nutrition, metabolism, and cardiovascular diseases : NMCD. 2010;20:186-94. 21. Campbell NR, Lackland DT and Niebylski ML. 2014 Dietary Salt Fact Sheet of the World Hypertension League, International Society of Hypertension, Pan American Health Organization Technical Advisory Group on Cardiovascular Disease Prevention Through Dietary Salt Reduction, the World Health Organization Collaborating Centre on Population Salt Reduction, and World Action on Salt & Health. Journal of clinical hypertension (Greenwich, Conn). 2014.

19

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

22. World Health Organization (WHO). Sodium intake for adults and children guideline. 2012. Available from: http://www.who.int/nutrition/publications/guidelines/sodium_intake_printversion.pdf. 23. Mente A, O'Donnell MJ, Rangarajan S, McQueen MJ, Poirier P, Wielgosz A, Morrison H, Li W, Wang X, Di C, Mony P, Devanath A, Rosengren A, Oguz A, Zatonska K, Yusufali AH, Lopez-Jaramillo P, Avezum A, Ismail N, Lanas F, Puoane T, Diaz R, Kelishadi R, Iqbal R, Yusuf R, Chifamba J, Khatib R, Teo K and Yusuf S. Association of urinary sodium and potassium excretion with blood pressure. N Engl J Med. 2014;371:601-11. 24. Mozaffarian D, Fahimi S, Singh GM, Micha R, Khatibzadeh S, Engell RE, Lim S, Danaei G, Ezzati M and Powles J. Global sodium consumption and death from cardiovascular causes. N Engl J Med. 2014;371:624-34. 25. Oparil S. Low sodium intake--cardiovascular health benefit or risk? N Engl J Med. 2014;371:677-9. 26. Committee on the Consequences of Sodium Reduction in P, Food, Nutrition B, Board on Population H, Public Health P and Institute of M. In: B. L. Strom, A. L. Yaktine and M. Oria, eds. Sodium Intake in Populations: Assessment of Evidence Washington (DC): National Academies Press (US) Copyright 2013 by the National Academy of Sciences. All rights reserved.; 2013. 27. O'Brien E, Parati G, Stergiou G, Asmar R, Beilin L, Bilo G, Clement D, de la Sierra A, de Leeuw P, Dolan E, Fagard R, Graves J, Head GA, Imai Y, Kario K, Lurbe E, Mallion JM, Mancia G, Mengden T, Myers M, Ogedegbe G, Ohkubo T, Omboni S, Palatini P, Redon J, Ruilope LM, Shennan A, Staessen JA, vanMontfrans G, Verdecchia P, Waeber B, Wang J, Zanchetti A and Zhang Y. European Society of Hypertension position paper on ambulatory blood pressure monitoring. Journal of hypertension. 2013;31:1731-68. 28. Jenkins DJ, Kendall CW, Marchie A, Faulkner DA, Wong JM, de Souza R, Emam A, Parker TL, Vidgen E, Lapsley KG, Trautwein EA, Josse RG, Leiter LA and Connelly PW. Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and Creactive protein. JAMA. 2003;290:502-10. 29. Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Aros F, Gomez-Gracia E, RuizGutierrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pinto X, Basora J, Munoz MA, Sorli JV, Martinez JA and Martinez-Gonzalez MA. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368:1279-90. 30. Yokoyama Y, Nishimura K, Barnard ND, Takegami M, Watanabe M, Sekikawa A, Okamura T and Miyamoto Y. Vegetarian diets and blood pressure: a meta-analysis. JAMA internal medicine. 2014;174:577-87.

20

ACCEPTED MANUSCRIPT

TABLE Table 1. Anthropometric and serum measures of portfolio and control diets, and the between-treatment differences. Pooled Portfolio (N=159)

27(26,27)

Waist (cm)

90(88,91)

TC (mmol/L)

6.5(6.4,6.7)

LDL-C (mmol/L) HDL (mmol/L)

Portfolio minus Control *

Difference -0.1(-1,0.9)

-0.7(-0.8.-0.5)

*

27(26,28)

-0.7(-0.9,-0.4)

*

0(-0.3,0.3)

0.992

0(-0.2,0.2)

-1(-1.4,-0.5)

*

90(88,93)

-1.3(-1.9,-0.7)

*

0.4(-0.4,1.1)

0.328

0.2(-0.4,0.8)

-0.8(-1.0,-0.7)

*

6.3(6.2,6.5)

-0.2(-0.3,0)

*

-0.7(-0.9,-0.5)

<.0001

-0.6(-0.7,-0.4)

<.0001

4.5(4.3,4.6)

-0.8(-0.9,-0.7)

*

4.3(4.1,4.4)

-0.2(-0.3,0)

*

-0.6(-0.8,-0.5)

<.0001

-0.5(-0.7,-0.4)

<.0001

1.4(1.4,1.5)

0(-0.1,0)

*

1.4(1.3,1.5)

0(-0.1,0)

0(-0.1,0.1)

TC:HDL

4.9(4.7,5.1)

-0.5(-0.6,-0.4)

*

4.8(4.5,5)

0(-0.2,0.1)

-0.5(-0.7,-0.3)

TG (mmol/L)

1.5(1.4,1.6)

0(-0.1,0.1)

1.5(1.3,1.8)

0(-0.1,0.1)

0(-0.2,0.1)

0.808

0(-0.2,0.1)

0.489

SBP (mmHg)

120(118, 122)

-2.5(-3.7,-1.2)

*

118(115, 121)

-0.4(-2.1,1.4)

-2.1(-4.2,0.1)

0.056

-2(-4,0)

0.045

DBP (mmHg)

73(72,75)

-2.0(-2.8,-1.2)

*

72(70,74)

-0.2(-1.4,0.9)

-1.8(-3.2,-0.4)

0.013

-1.3(-2.6,-0.1)

0.039

MAP (mmHg)

89(87,90)

-2.1(-3.0,-1.3)

*

87(85,89)

-0.3(-1.5,1)

-1.9(-3.4,-0.4)

0.015

-1.6(-2.9,-0.2)

0.026

Apo-A1 (g/L)

1.6(1.6,1.6)

0(0,0)

1.6(1.6,1.7)

0(0,0)

0(0,0)

0.926

0(0,0)

Apo-B (g/L)

1.2(1.2,1.3)

-0.2(-0.2,-0.1)

1.2(1.1,1.2)

0(0,0)

CRP (mg/L) †

1.5(1.3,1.8)

-0.2(-1.0,0.5)

10 yr CHD Risk

8(7.3,8.6)

-1.4(-1.7,-1.1)

* *

10 yr CVD Risk

9.9(9.0,10.8)

-1.6(-1.9,-1.2)

*

*

Pr > |t| 0.857

Adjusted‡ -0.1(-0.1,0)

*

Change -1.8(-2.6,-1)

RI PT

BMI (kg/m2)

Control (N=82) Baseline 76(73,79)

0.923

<.0001

SC

Change -1.9(-2.4,-1.3)

-0.2(-0.2,-0.1)

M AN U

Weight (kg)

Baseline 75(73,77)

<.0001

2.3(1.1,3.4)

0.5(-0.4,1.5)

-0.8(-2.0,0.4)

7.3(6.4,8.2)

-0.2(-0.6,0.2)

-1.2(-1.7,-0.7)

0.007 <.0001

9.2(8,10.4)

-0.2(-0.7,0.3)

-1.4(-2,-0.8)

<.0001

0(-0.1,0)

-0.4(-0.6,-0.3)

-0.1(-0.2,-0.1) -1.3(-2.5,-0.2)

Pr > |t| 0.237 0.838 0.472

0.831 <.0001

0.988 <.0001

-1(-1.4,-0.6)

0.000 <.0001

-1.2(-1.7,-0.7)

<.0001

Data are presented as mean, confidence interval All post intervention estimates are least square means. Model is mixed with repeated measures, using compound symmetry as a covariance structure. ‡ Covariates: Waist, BMI, age, sex, blood pressure medica$on, baselines. † P-values based on log transformed data.

AC C

EP

TE D

* represents significance at p<0.05.

ACCEPTED MANUSCRIPT

Table 2. Change in Dietary Variables versus Change in Blood Pressure, CHD, and CVD Risk. Coronary Heart Disease (CHD) Risk ρ p-value -0.04 0.51

Cardiovascular Disease (CVD) Risk ρ p-value -0.02 0.81

0.02 -0.19 -0.10 0.12 -0.14 -0.18 0.11

0.79 0.003 0.14 0.07 0.025 0.006 0.10

-0.03 -0.16 -0.09 0.12 -0.15 -0.18 0.08

0.67 0.015 0.15 0.06 0.017 0.006 0.24

-0.08 -0.31 -0.25 0.16 -0.27 -0.30 0.14

0.24 <.0001 0.000 0.014 <.0001 <.0001 0.026

-0.06 -0.31 -0.22 0.18 -0.26 -0.30 0.16

0.36 <.0001 0.001 0.005 <.0001 <.0001 0.012

0.07 0.08 -0.15

0.31 0.24 0.016

0.04 0.10 -0.13

0.52 0.11 0.045

0.01 0.27 -0.19

0.88 <.0001 0.004

0.00 0.25 0.21

0.99 <.0001 0.001

-0.17

0.010

-0.17

-0.16

0.011

-0.15

-0.12 0.09 -0.03 0.10 -0.18 -0.03

SC

RI PT

Mean Arterial Pressure (MAP) ρ p-value -0.01 0.94

0.009

-0.33

<.0001

-0.35

<.0001

0.016

-0.31

<.0001

-0.31

<.0001

0.07

-0.11

0.10

-0.21

0.001

-0.24

0.000

0.18

0.08

0.22

0.08

0.22

0.09

0.16

0.61 0.14

0.07 0.12

0.31 0.06

0.04 0.06

0.58 0.36

-0.04 0.11

0.58 0.09

0.006

-0.16

0.011

-0.33

<.0001

-0.34

<.0001

0.66

-0.05

0.44

0.09

0.16

0.05

0.46

AC C

EP

TE D

Dietary Variable Total Calories (kcal) Protein (%) -0.09 0.19 Soy Protein (%) -0.09 0.15 Fat (%) -0.07 0.28 SFA (%) 0.10 0.11 MUFA (%) -0.13 0.038 PUFA (%) -0.14 0.030 Cholesterol 0.04 0.58 (mg/1000 kcal) Alcohol (%) 0.02 0.81 Net CHO (%) 0.10 0.11 Total Fiber -0.08 0.23 (g/1000 kcal) Viscous Fiber -0.14 0.034 (g/1000 kcal) Nuts (g/1000 -0.11 0.09 kcal) Plant Sterols -0.06 0.39 (g/1000 kcal) Na+ (mg/1000 0.05 0.45 kcal) K+ (mg/1000 kcal) -0.10 0.13 Na+/K+ 0.14 0.032 Portfolio Adherence -0.11 0.08 DASH Adherence -0.08 0.24 Data presented are Spearman correlations.

Diastolic Blood Pressure (DBP) ρ p-value -0.04 0.54

M AN U

Systolic Blood Pressure (SBP) ρ p-value 0.04 0.56

22

ACCEPTED MANUSCRIPT

FIGURE LEGEND Figure 1. Changes in systolic (A), diastolic (B), and mean arterial pressure (MAP) (C) in

AC C

EP

TE D

M AN U

SC

RI PT

Portfolio and Control diets at weeks 0, 12, and 24.

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

FIGURES Figure 1. Changes in systolic (A), diastolic (B), and mean arterial pressure (MAP) (C) in Portfolio and Control diets at weeks 0, 12, and 24. * represents significance at P<0.05.

ACCEPTED MANUSCRIPT

The Effect of a Dietary Portfolio Compared to a DASH-Type Diet on Blood Pressure Highlights

RI PT

SC




M AN U




TE D




EP




The DASH diet has become generally accepted as a hypertension and cardiovascular risk reduction strategy. The Dietary Portfolio was developed specifically as a LDL-cholesterol reducing diet, but has food components that also lower blood pressure. A previously published multi-centre study confirmed that cholesterol –lowering approach of the Dietary Portfolio and suggested the possibility for a blood pressure effect. We have therefore reassessed the previously published study from the standpoint of compliance with either a DASH (control) or Portfolio (test) diet in relation to blood pressure with detailed dietary and urinary analysis (including minerals). This study has strengthened the case that both the DASH and the Portfolio diets have blood pressure and cardiovascular risk reduction potential.

AC C




ACCEPTED MANUSCRIPT

Supplemental Figure 1. Flow diagram of participants in the study.

351 Randomized

RI PT

879 Individuals Assessed for Eligibilitya

TE D

223 Randomized to Receive Intensive (n=101) or Routine (n=122) Portfolio

M AN U

SC

345 Included in Primary Analysis 6 Excluded 3 Did not start 3 Randomized in error

EP

177 Completed Trial

AC C

159 Included in Completer Analysis of Intensive (n=75) and Routine (n=84) Portfolio*

122 Randomized to Receive Control

90 Completed Trial

82 Included in Completer Analysis of Control*

*The original consort statement includes reasons for exclusion (Jenkins et al., 2011). †Completed both the original study and provided 7-day diet histories at the start and end of the study period

ACCEPTED MANUSCRIPT The Effect of a Dietary Portfolio Compared to a DASH-Type Diet on Blood Pressure, Jenkins et al

SUPPLEMENTARY TABLES

Start

End

RI PT

Supplemental Table 1a. Adherence assessed as mean (SD) number of recommended Dietary Portfolio food group servings consumed on the Dietary Portfolio and Control diets, adjusted for 2000 kcal diet Control Control Dietary Dietary Dietary Portfolio Portfolio Portfolio Diet Diet Recommended Start End Number of Servings*

Servings

0.2(0.3)

0(0.2)

0.3(0.5)

2.7(1.9)

7.0

Viscous Fiber

0.3(0.5)

0.2(0.4)

0.3(0.5)

3.4(2.4)

7.0

Nuts

0.6(0.5)

0.2(0.3)

0.4(0.4)

1.1(0.6)

1.5

Plant sterols

0(0)

0(0)

0(0)

Total # Servings

1.0(0.9)

0.4(0.6)

2.6(2.1)

5.0

9.9(5.3)

20.5

M AN U

1.0(0.9)

SC

Soy protein

AC C

EP

TE D

% of Recommended 4.8(4.5) 1.8(2.7)† 4.9(4.5) 48.3(25.8)ǂ 100 *Soy protein serving = 1 cup soy beverage (light or fortified), ¼ cup tofu (extra firm, low fat), 4 soy deli slices, 1 soy burger, 1 soy hot dog; Viscous Fiber serving = ½ cup (dry) oat bran, 1 slice oat bran bread, ¼ cup (dry) barley, 2 tsp psyllium husk, ½ cup (frozen) okra, 2 cups (raw) eggplant; Nut serving = 1 handful almonds (or 24 nuts); Plant sterols serving = 1 tsp Pro-activ spread. †Significantly different from baseline ‡Significantly different from control end Each component (soy protein, viscous fibre, nuts, and plant sterols) in the amount recommended contributes 25% to the score of 100% adherence.

6

ACCEPTED MANUSCRIPT The Effect of a Dietary Portfolio Compared to a DASH-Type Diet on Blood Pressure, Jenkins et al

Supplemental Table 1b. Adherence assessed as mean (SD) number of DASH diet food group servings consumed by Dietary Portfolio and DASH-Type Control††† diets, adjusted for 2000 kcal diet. DASH-Type Control Diet, End

Portfolio Diet, Start

Portfolio Diet, End

OmniCarb‡‡‡ DASH, mean (range)

Counted Positively in DASH total: Fruits & Juices ‡ Vegetables§ Low-Fat Dairy ǁ

3.3 (1.7) 5.3 (2.5) 1.1 (0.9)

5.0 (5.0) 6.7 (3.3) 2.2 (1.3)

3.2 (1.7) 4.9 (3.5) 1.1 (0.9)

3.4 (2.1) 4.7 (2.6) 0.3 (0.5)

5.6 (4.1-7.0) 4.7 (3.6-6.4) 2.6 (2.2-3.0

Counted Negatively in DASH total: Beef, Ham, & Other Pork ¶ Snack foods and sweets**

0.5 (0.4) 1.2 (1.7)

0.2 (0.3) 0.8 (1.1)

0.5 (0.4) 1.0 (1.5)

0.2 (0.4) 0.9 (1.5)

0.5 (0.2-0.8) 0.2 (0.1-0.3)

Not counted in DASH total: Grains†† Egg whites and egg substitutes‡‡ Fats, Oils, and Salad Dressing§§

7.3 (2.8) 0.4 (0.3) 2.5 (1.6)

8.4 (3.0) 0.6 (0.8) 3.0 (2.0)

7.6 (3.0) 0.4 (0.4) 2.5 (1.8)

9.0 (5.1) 0.1 (0.4) 4.7 (4.6)

7.2 (4.8-9.0) 0.4 (0.0-0.9) 6.8 (5.9-7.8)

Total servings*** % of OmniCarb DASH average

8.7 (4.1) 68 (32)

13.6 (7.2) 105 (56)*

8.4 (4.6) 65 (36)

8.0 (4.4) 62 (34)†

12.9 100

RI PT

DASH-Type Control Diet, Start

SC

Food Group (no. of servings per day)

AC C

EP

TE D

M AN U

*Significantly different from baseline (P<0.05). †Significantly different from control end ‡serving=6 oz fruit juice, 1 medium fruit, ¼ cup dried fruit, ½ cup fresh, frozen or canned fruit §serving = 1 cup raw leafy vegetable, ½ cup cooked vegetable, 6 oz vegetable juice ǁ serving = 8 oz milk, 1 cup yogurt, 1.5 oz cheese ¶ serving = 3 oz cooked **serving = 1 Tbsp sugar, 1 Tbsp jam, 8 oz sugar-sweetened beverage ††serving = 1 slice bread, 1 oz dry cereal, ½ cup cooked rice, pasta, cereal ‡‡serving = 1 egg equivalent (50g) §§serving = 1 tsp margarine, 1 Tbsp mayonnaise, 2 Tbsp salad dressing, 1 tsp vegetable oil ***Calculated as [Fruits & Juices] + [Vegetables] + [Low-fat Dairy] – ([Beef, Ham, & Other Pork]-0.5) – ([Snack foods and sweets]-0.2) ††† Control diet recommended servings: 5 Fruits & Juices, 5 Vegetables, 4 Low-Fat Dairy, 7 Grains, 3 Egg whites/substitutes, 4 Fats/oils. ESHA Food Processor SQL was used in the dietary analysis and determination of intake. ‡‡‡ The prescribed 12.9 portions of fruits, vegetables, and low fat dairy for 2000 kcals reported in the recent OmniCarb DASH study represent 100% adherence, to which fruit, vegetables and low fat dairy contribute positively and meats and snack food contribute negatively (7.75% per serving).12

ACCEPTED MANUSCRIPT The Effect of a Dietary Portfolio Compared to a DASH-Type Diet on Blood Pressure, Jenkins et al

Supplemental Table 2. Changes in anthropometric and serum measures between Pooled Dietary Portfolio and the DASH-Type Control diet at weeks 12 and 24 separately. Pr>|t| 0.87 0.99 0.24 <.0001 <.0001 0.287 <.0001 0.90 0.17 0.28 0.19 0.53 <.0001 0.010 <.0001 <.0001

0.0 0.1 0.1 -0.55 -0.55 0.03 -0.54 -0.04 -1.2 -0.4 -0.7 0.01 -0.14 -0.8 -1.2 -1.3

Adjusted* (-0.1,0.1) (-0.1,0.3) (-0.4,0.7) (-0.74,-0.36) (-0.71,-0.38) (-0.03,0.08) (-0.74,-0.35) (-0.20,0.13) (-3.5,1.0) (-2.0,1.2) (-0.03,0.05) (-0.03,0.05) (-0.17,-0.10) (-1.5,-0.2) (-1.7,-0.7) (-1.9,-0.6)

Pr>|t| 0.63 0.37 0.63 <.0001 <.0001 0.350 <.0001 0.66 0.28 0.62 0.42 0.66 <.0001 0.0004 <.0001 0.0001

Pr>|t| 0.86 0.98 0.49 <.0001 <.0001 0.32 0.0002 0.45 0.062 0.002 0.005 0.52 <.0001 0.051 0.0001 0.0002

AC C

EP

TE D

M AN U

Data are presented as mean (95% confidence interval) All differences are least squares means. *Covariates: waist, BMI, age, sex, blood pressure medication, baselines. †P-values taken from log transformed data.

Week 24 Difference -0.1 (-1.0,0.8) 0.0 (-0.3,0.3) 0.3 (-0.6,1.2) -0.70 (-0.92,-0.48) -0.61 (-0.80,-0.41) -0.03 (-0.09,0.03) -0.41 (-0.62,-0.19) -0.06 (-0.23,0.10) -2.4 (-4.8,0.1) -2.6 (-4.2,-1.0) -2.5 (-4.2,-0.8) -0.01 (-0.05,0.03) -0.16 (-0.20,-0.11) -1.2 (-3.3,0.9) -1.1 (-1.6,-0.5) -1.3 (-1.9,-0.6)

-0.1 0.0 0.2 -0.60 -0.53 -0.03 -0.38 -0.06 -2.6 -2.2 -2.4 -0.01 -0.13 -1.9 -0.9 -1.1

Adjusted* (-0.2,0.0) (-0.3,0.2) (-0.5,0.9) (-0.79,-0.42) (-0.70,-0.36) (-0.09,0.03) (-0.57,-0.18) (-0.20,0.08) (-5.0,-0.2) (-3.7,-0.8) (-4.0,-0.7) (-0.05,0.03) (-0.17,-0.09) (-4.0,0.3) (-1.4,-0.5) (-1.7,-0.5)

Pr>|t| 0.18 0.89 0.56 <.0001 <.0001 0.26 0.0002 0.41 0.033 0.003 0.005 0.53 <.0001 0.012 <.0001 0.0001

RI PT

Week 12 Difference -0.1 (-1.3,1.1) 0.0 (-0.4,0.4) 0.4 (-0.3,1.1) -0.67 (-0.89,-0.44) -0.68 (-0.87,-0.48) 0.03 (-0.03,0.09) -0.59 (-0.80,-0.37) 0.01 (-0.17,0.20) -1.7 (-4.0,0.7) -0.9 (-2.6,0.7) -1.2 (-2.9,0.6) 0.01 (-0.03,0.05) -0.16 (-0.20,-0.12) -0.4 (-1.2,0.5) -1.4 (-2.0,-0.8) -1.5 (-2.2,-0.8)

SC

Variable Weight (kg) BMI (kg/m2) Waist (cm) TC (mmol/L) LDL (mmol/L) HDL (mmol/L) TC:HDL TG (mmol/L) SBP (mmHg) DBP (mm/Hg) MAP (mmHg) Apo-A1 (g/L) Apo-B (g/L) CRP (mg/L) † 10 yr CHD Risk 10 yr CVD Risk

ACCEPTED MANUSCRIPT The Effect of a Dietary Portfolio Compared to a DASH-Type Diet on Blood Pressure, Jenkins et al

Supplemental Table 3. Dietary measures of Portfolio and Control Diets, and between-treatment difference.

EP AC C

Difference Pr > |t| 80(-31, 190) 0.16 0.2(-0.7,1.1) 0.68 3.4(2.8,3.9) <.0001 8.3(6.5,10) <.0001 -1.0(-1.7,-0.3) 0.008 4.3(3.3,5.3) <.0001 3.8(3.2,4.5) <.0001 -28(-42,-14) <.0001 -7.7(-9.5,-5.8) <.0001 5.4(3.7,7) <.0001 -0.8(-1.5,0) 0.039 4.6(3.8,5.3) <.0001 17(15,20) <.0001 0.5(0.4,0.6) <.0001 -50(-155,54) 0.34 -127(-242,-12) 0.031 0(-0.1,0.1) 0.87

RI PT

SC

-0.1(-1.4,1.1) -0.1(-0.5,0.3) 0(-0.2,0.2)

TE D

Urinary Measures 13.3(12.3,14.3) Urinary Na+ / Creatinine Urinary K+ / Creatinine 6.9(6.5,7.3) Urinary Na/K 2.1(1.9,2.3) Data are presented as mean (95% confidence interval) Difference is adjusted using Least Square Means * Significant change from baseline (P<0.05).

Control (Ns = 82 diet, 55 urine) Week 0 Change 1818(1717, 1918) -148(-238,-58)* 19(18,19) 0.5(-0.3,1.2) 0.2(0.1,0.3) -0.2(-0.6,0.3) 31(30,32) -6.1(-7.6,-4.7)* 8.7(8.2,9.2) -1.8(-2.4,-1.2)* 11(11,12) -2.2(-3,-1.4)* 6.3(5.9,6.7) -0.7(-1.2,-0.1)* 116(107, 126) -36(-47,-25)* 48(47,50) 5.9(4.4,7.4)* 16(15,17) 3.6(2.2,4.9)* 2.5(1.8,3.2) -0.2(-0.8,0.4) 0.4(0.2,0.5) -0.1(-0.8,0.5) 8.3(6.5,10) -5.9(-8,-3.7)* 0(0,0) 0(-0.1,0.1) 1360(1289, 1432) -13(-98,72) 1851(1751, 1951) 291(198, 385)* 0.8(0.7,0.8) -0.1(-0.2,-0.1)*

13.7(11.8,15.6) 6.9(6.2,7.6) 2.1(1.8,2.3)

-0.1(-1.9,1.6) 0.8(0.2,1.4)* 0(-0.3,0.2)

M AN U

Dietary Measures Total Calories (kcal) Total Protein % Soy Protein % Fat % SFA % MUFA % PUFA % Chol mg/ 1000 kcal Net Carbohydrate % Fiber g/1000 kcal Alcohol % Viscous fiber g/1000 kcal Nuts g/1000 kcal Plant sterol g/1000 Sodium g/1000 kcal Potassium g/1000 Na/K

Pooled Portfolio (Ns = 159 diet, 109 urine) Week 0 Change 1894(1820, 1968) -68(-132,-3.3)* 18(17,18) 0.6(0.1,1.2)* 0.4(0.3,0.5) 3.2(2.9,3.5)* 31(30,31) 2.1(1.1,3.2)* 9.2(8.7,9.7) -2.8(-3.3,-2.4)* 11(10,11) 2.1(1.5,2.7)* 5.9(5.6,6.2) 3.1(1.5,2.7)* 118(110, 126) -64(2.8,3.5)* 49(48,50) -1.8(-2.9,-0.7)* 15(14,15) 8.9(8,9.9)* 3.1(2.6,3.6) -1.0(-1.4,-0.6)* 0.5(0.4,0.6) 4.5(4,4.9)* 6.1(5.1,7.2) 12(10,13)* 0(0,0) 0.5(0.5,0.6)* 1368(1317, 1420) -63(-124,-2.4)* 1748 (1687, 1810) 164(97, 231)* 0.8(0.8,0.9) -0.1(-0.2,-0.1)*

0(-2.2,2.2) -0.9(-1.6,-0.2) 0.1(-0.3,0.4)

0.99 0.016 0.71

ACCEPTED MANUSCRIPT The Effect of a Dietary Portfolio Compared to a DASH-Type Diet on Blood Pressure, Jenkins et al

Supplemental Table 4. Change in compliance versus change in blood pressure, CHD, and CVD risk within each treatment group. Diastolic Blood Pressure (DBP) ρ p-value

Mean Arterial Pressure (MAP) ρ p-value

0.02 -0.05

0.83 0.56

0.02 -0.08

0.84 0.30

0.01 -0.07

0.89 0.37

-0.14 0.00

0.07 0.95

-0.21 0.01

0.010 0.93

DASH-Type Diet Participants Only Portfolio Adherence -0.16 DASH Adherence -0.35 Data presented are Spearman correlations.

0.15 0.001

-0.18 -0.24

0.11 0.033

-0.19 -0.30

0.09 0.005

-0.19 -0.09

0.09 0.41

-0.22 -0.22

0.051 0.043

AC C

EP

TE D

M AN U

SC

Dietary Variables Portfolio Diet Participants Only Portfolio Adherence DASH Adherence

Coronary Heart Disease (CHD) Risk ρ p-value

Cardiovascular Disease (CVD) Risk ρ p-value

RI PT

Systolic Blood Pressure (SBP) ρ p-value