To determine the effect on blood pressure of dietary advice to consume a combination of plant-based cholesterol-lowering foods (dietary portfolio).
For 1 year, 66 hyperlipidemic subjects were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal) and almonds (22.5 g/1000 kcal). There was no control group. Seven-day diet record, blood pressure and body weight were monitored initially monthly and later at 2-monthly intervals throughout the study.
Fifty subjects completed the 1-year study. When the last observation was carried forward for non-completers (n=9) or those who changed their blood pressure medications (n=7), a small mean reduction was seen in body weight 0.7±0.3 kg (P=0.036). The corresponding reductions from baseline in systolic and diastolic blood pressure at 1 year (n=66 subjects) were −4.2±1.3 mm Hg (P=0.002) and −2.3±0.7 mm Hg (P=0.001), respectively. Blood pressure reductions occurred within the first 2 weeks, with stable blood pressures 6 weeks before and 4 weeks after starting the diet. Diastolic blood pressure reduction was significantly related to weight change (r=0.30, n=50, P=0.036). Only compliance with almond intake advice related to blood pressure reduction (systolic: r=−0.34, n=50, P=0.017; diastolic: r=−0.29, n=50, P=0.041).
A dietary portfolio of plant-based cholesterol-lowering foods reduced blood pressure significantly, related to almond intake. The dietary portfolio approach of combining a range of cholesterol-lowering plant foods may benefit cardiovascular disease risk both by reducing serum lipids and also blood pressure.
The success of diet and lifestyle modification in reducing blood pressure has renewed interest in non-pharmacological approaches to control hypertension (Appel et al., 1997, 2003; Sacks et al., 1999; Svetkey et al., 2005). Before the publication of the benefits of the DASH diet (Appel et al., 1997; Dwyer et al., 1998; Sacks et al., 1999; Lin et al., 2003), rapid growth in the number of effective drugs developed for the control of hypertension had been a major factor resulting in a relative lack of enthusiasm for employing dietary approaches for blood pressure control. However, the demonstration that application of diet could result in blood pressure reductions similar to the starting dose of drug monotherapy renewed interest in diet as an important component of hypertension control (Appel et al., 1997, 2003; Sacks et al., 1999; Svetkey et al., 2005).
We have recently explored the use of a vegetarian diet, combining four groups of cholesterol-lowering components of plant origin, viscous fibers, soy protein, plant sterols and almonds (dietary portfolio) in an attempt to maximize the effect of diet in blood lipid reduction (Jenkins et al., 2002, 2003, 2005). Since, in addition to lipid reduction, at least two of these components had potential blood pressure lowering properties (Dodson, 1980; Rivas et al., 2002; Jenkins et al., 2002; Kreijkamp-Kaspers et al., 2005; Streppel et al., 2005), we also considered it of interest to assess the effect of this diet on blood pressure as a key modifiable factor which together with blood lipids contribute to coronary heart disease (CHD) risk. The blood lipid data have been reported (Jenkins et al., 2006).
Sixty-six hyperlipidemic participants were recruited (Table 1). Of these, 24 men and 26 postmenopausal women completed the 1-year study, whereas 16 participants did not complete the study (Figure 1). The participants were largely of European origin (n=54). There were also five Chinese participants, four East Indian, two Black and one Hispanic participant. Most of the subjects were recruited by newspaper advertisement (Figure 1). Blood lipid data on the ad libitum study have been submitted for publication. Participants' baseline characteristics are shown in Table 1. At screening, all participants had raised low-density lipoprotein-cholesterol levels (>4.1 mmol/l) (Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, 2001). No participants had a history of cardiovascular disease, diabetes, renal or liver disease. At recruitment, four subjects had untreated hypertension (blood pressure at or above 140/90 mm Hg), two of whom showed blood pressure reductions below 140/90 mm Hg during the study without medication. Eight participants were taking antihypertensive medications at a constant dose before and during the study. One started antihypertensive medication during the study. Four altered the dosage and/or number of antihypertensive medications taken during the study: two added a new medication or increased the dosage of an existing medication, one reduced the dosage and one changed medication.
The intervention was a single-phase 1-year open label study of a self-selected (ad libitum) dietary portfolio of cholesterol lowering foods. All subjects were instructed to follow a step 2 diet for 2 months before commencing the 1-year study. During the 1-year study, participants were seen at weeks 0, 2, 4, 8, 12, 18±2, 24, 32, 42 and 52. At each visit, fasting body weights were checked and blood samples were obtained after 12 h overnight fasts. Blood pressure was measured twice in the non-dominant arm using a mercury sphygmomanometer by the same observer after subjects had been seated for at least 15 min and the average blood pressure was used. Seven-day diet histories were obtained for the week before the clinic visit and checked by the dietitian. The records were discussed with the dietitian and suggestions made to enhance compliance. The previous week's exercise was also recorded and the dietitian encouraged each participant to hold this constant over the pre-study and study periods. Compliance was assessed from the 7-day diet histories.
The Ethics Committee of St Michael's Hospital and the Therapeutic Products Directorate of Health, Canada approved the study. Written informed consent was obtained from the participants.
Before the study, participants were instructed to eat their routine therapeutic low-fat diets with mean macronutrient profiles (Table 2), which were close to current National Cholesterol Education Program adult treatment panel III (NCEP ATP III) guidelines (<7% energy from saturated fat and <200 mg/day dietary cholesterol) (Jenkins et al., 2006).
Dietary advice for the 1-year ad libitum study was based on the consumption goals for the same four dietary components, which had been emphasized in previous metabolic dietary portfolio studies (Jenkins et al., 2002, 2003, 2005). Participants were advised to consume 1.0 g plant sterols per 1000 kcal of diet from a plant sterol ester-enriched margarine; approximately 10 g viscous fibers per 1000 kcal of diet from oats, barley, psyllium and the vegetables, okra and eggplant; 22.5 g soy protein per 1000 kcal as soy milk and soy meat analogues, and 22.5 g whole almonds per 1000 kcal of diet in addition to their ongoing low-fat diet. To the extent acceptable to participants, advice was given to take a vegetarian diet without the use of dairy foods or eggs. This dietary portfolio has been described in detail previously (Jenkins et al., 2002, 2003, 2005).
Self-taring electronic scales (Salter Housewares, Kent, England) were provided to all participants. They were asked to weigh all food items consumed in the week when diet histories were recorded.
Adherence to the ad libitum dietary portfolio was assessed from the completed 7-day food records.
Diets were analyzed for macronutrients, fatty acids, cholesterol and fiber using a computer program based on US Department of Agriculture data (The Agricultural Research Service, 1992).
The results are expressed as mean±s.e. Differences between weeks 0 and 52 were assessed by Student paired t-test (two-tailed). Intention to treat analysis was carried out with last value carried forward for subjects who dropped out or changed blood pressure medications. The effect of change over time from baseline was also assessed using a generalized linear mixed model, with spatial power covariance to adjust for unequal sampling periods (weeks 2, 4, 8, 12, 18±2 and 24, 32, 42, and 52). This repeated measures analysis had blood pressure change from week 0 as the response variable and week as the covariate predictor, with subject ID as the sole class variable (SUBJECT option in REPEATED statement). The cohort of 66 subjects were further divided into three groups of approximately equal size based on body weight reduction to the nearest half kilogram from baseline to 1 year (i.e. Group 1, >1.5 kg; Group 2, 1.5, 0 kg; Group 3, <0 kg). Subjects were also divided into higher and lower blood pressures using the 130/85 cut-point employed by NCEP ATP III in the definition of the metabolic syndrome (Grundy et al., 2004).
The significance of the differences in macronutrients between weeks 0, 24 and 52, as well as blood pressure for week −6 to week 4 of the diet, were assessed by least squares means (SAS Institute, 1997) with Tukey–Kramer adjustment for multiple pair-wise comparisons. In the least squares means assessment, the model had measured macronutrient level or blood pressure as the response variable with timeline (week) as the main effect and with subject's ID as the random effect indicating the crossover aspect of the experimental design.
Associations between blood pressure and body weight reductions with different compliance measures were calculated based on the mean 2–52 week values for compliance measures and the difference from time zero of the mean 2–52 week values for blood pressure and body weight using Pearson's correlation (SAS Institute, 1997). Compliance was assessed for individual components where the prescribed amount represented 100%. The total compliance was the sum of the individual compliances given equal weighting.
Over the 1 year of the ad libitum dietary portfolio a small weight loss was observed (−0.7±0.3 kg, n=66, P=0.036).
Blood pressure readings were constant for the three clinic visits during the 6 weeks before starting the study. For the whole group (n=66), near maximum reductions in blood pressure were seen at 2 weeks on the diet (systolic −6.4±1.3 mm Hg, P<0.001; diastolic −3.2±0.7 mm Hg, P<0.001) and significant reductions were sustained to 1 year, (systolic −4.2±1.3 mm Hg, P=0.002; diastolic −2.3±0.7 mm Hg, P=0.001; Table 3). Similar reductions were seen at 1 year in the 50 subjects who completed the 1-year diet without changes in blood pressure medications (systolic −5.3±1.5 mm Hg, P=0.001; diastolic −2.3±0.8 mm Hg, P=0.008). These reductions in turn were very similar to those seen in the completers who did not take blood pressure medications during the study (systolic −5.7±1.4 mm Hg, P<0.001; diastolic −2.4±0.9 mm Hg, P=0.009). No significant differences in blood pressure reduction were seen between the sexes. No significant time trends were seen for changes from baseline for both systolic and diastolic blood pressure. In addition, pre-treatment blood pressures showed no downward trend compared with baseline. The first significant reduction in blood pressure occurred between time zero and week 2 of the treatment. Data to illustrate these points, including pre-study values and the first 4 weeks of the study period, are shown for both systolic and diastolic blood pressure (Figure 2). For systolic blood pressure, no difference was seen between the week −6, −2 and zero values before the start of the diet, as assessed by least squares means with a Tukey adjustment for multiple comparisons, or between weeks 2 and 4 on the diet (P>0.966). A similar lack of difference was seen for diastolic blood pressure. However, all pre-diet values were significantly different from the post-diet values (systolic blood pressure P<0.007 and diastolic blood pressure P=0.001). These data indicate that it was the diet and not the clinic attendance, which was associated with the blood pressure reduction on the study.
Subjects on the ad libitum portfolio study were also divided into groups based on their 1-year weight loss (Figure 3): those with body weight reductions from baseline >1.5 kg (Group 1, bottom panel); 1.5–0 kg (Group 2, middle panel) and those who showed a weight gain (Group 3, top panel). At 1 year, subjects with >1.5 kg weight loss (n=20/66) showed systolic and diastolic blood pressure reductions (−4.8±2.7 mm Hg, P=0.089; and −3.2±1.3 mm Hg, P=0.024). The respective figures for those with a weight loss no greater than 1.5 kg (n=22/66) and those with a weight gain (n=24/66) were systolic pressure −6.5±2.2 mm Hg (P=0.007) and −1.6± 1.8 mm Hg (P=0.400) and diastolic −3.1±1.1 mm Hg (P=0.009) and −0.9±1.1 mm Hg (P=0.441).
Compliance, body weight, blood pressure and mineral intake
The only significant compliance associations were seen between almond compliance and changes in systolic blood pressure (r=−0.34, n=50, P=0.017) and diastolic blood pressure (r=−0.29, n=50, P=0.041; Figure 4). Differences in mineral intake between week 0 and week 52 were significant for magnesium (P<0.001) and sodium (P=0.014; Table 4). The magnesium and potassium differences were negatively related to differences in diastolic blood pressure (r=−0.32, n=47, P=0.028 and r=−0.31, n=47, P=0.032, respectively). Changes in weight also related to the reduction in diastolic blood pressure (r=0.30, n=50, P=0.035), although the relation to reduction in systolic blood pressure did not reach significance (r=0.25, n=50, P=0.080). Compliance related to weight change (r=−0.31, n=50, P=0.026). Weight change also related to changes in viscous fiber, almond and soy compliances (r=−0.34, n=50, P=0.015; r=−0.31, n=50, P=0.026; r=−0.33, n=50, P=0.018, respectively). No other significant associations were found with blood pressure and weight change or compliance with other dietary components.
Effect of starting blood pressure and age
The reduction in systolic blood pressure (−13.2±1.7 mm Hg) in the 14/66 subjects with modestly raised blood pressure (130/85) was significantly greater (P<0.001) than the 52/66 with a normal blood pressure (−1.8±1.4 mm Hg). The respective figures for diastolic blood pressure were −7.1±1.0 mm Hg versus −1.0±0.7 mm Hg, respectively, (P<0.001). Those with greater elevations of blood pressure 140/90 (n=8) showed reductions in systolic blood pressure of −12.3±2.5 mm Hg (P=0.002) and reductions in diastolic blood pressure of −5.6±1.2 mm Hg (P=0.002).
For completers again, the subjects with elevated blood pressure (130/85) at baseline showed a greater reduction in systolic blood pressure at 1 year (−16.9±1.3 mm Hg, n=9, P<0.0001) than those with normal blood pressures (−2.8±1.6, n=41, P=0.088).
Blood pressure reduction related to age with older subjects showing a greater reduction in blood pressure than younger subjects (systolic blood pressure, r=−0.32, n=66, P=0.010; diastolic blood pressure, r=−0.34, n=66, P=0.006).
Application, under free-living real-world conditions, of a diet, which combined a variety of cholesterol-lowering foods resulted in a blood pressure reduction which was only partially explained by weight loss. Mean systolic blood pressure reductions of 4 mm Hg combined with a mean reduction in total:high-density lipoprotein-cholesterol of 13.3% (n=66) would translate into an approximate 20.3% reduction in CHD risk in this population using the Framingham cardiovascular disease predictive equation (Anderson et al., 1991).
The reduction in blood pressure could be a placebo effect resulting from frequent visits to the clinic since we have no formal control group with which to compare the test results. However, assessment of the blood pressure data for the three visits spanning a 6-week pre-study period indicate a stable blood pressure before the study. Furthermore, the first 2 weeks of the study saw the major blood pressure reduction after which blood pressure was relatively stable.
The fall in blood pressure related most strongly to age and pre-treatment blood pressure as reported in other studies (Weinberger and Fineberg, 1991; Whelton, 1998; Appel et al., 2003). The relation with weight loss was less strong owing to the small weight loss seen over 1 year (0.64 kg). For subjects with blood pressures greater than 130/85, the systolic blood pressure reduction of 13 mm Hg was similar to that reported for the DASH and PREMIER diets (Appel et al., 1997; Sacks et al., 1999; Chobanian et al., 2003), whereas those already with target blood pressures showed little effect. The blood pressure reductions were not altered when the seven completers on stable doses of blood pressure medication were removed. Change in alcohol consumption did not appear to be a factor since alcohol intake was reported to be very low and was constant across the study period.
Fiber and soy proteins have also been associated with blood pressure reduction, although the mechanisms have not been clearly defined (Dodson, 1980; Jenkins et al., 2002; Rivas et al., 2002; Kreijkamp-Kaspers et al., 2005; Streppel et al., 2005). Almonds and other nuts are rich sources of minerals (calcium, magnesium and potassium; Intersalt: an international study of electrolyte excretion and blood pressure, 1988; Griffith et al., 1999; Resnick et al., 2000), which have been associated with a beneficial effect on blood pressure (Food and Drug Administration Dockets Management 00Q-158, 2000; Jee et al., 2002; van Mierlo et al., 2006). This is the first study to date to implicate nuts, that is almonds, in blood pressure reduction. By way of explanation for the almond effect, the higher magnesium and to a lesser extent potassium intake on the dietary portfolio related to the reduction in diastolic blood pressure. When the R2 for systolic and diastolic blood pressure change, regressed against weight change were expressed as a percentage to estimate the influence of body weight on blood pressure, then weight change accounted for approximately 6% of the reduction in systolic blood pressure (R2=0.063) and 9% of the reduction in diastolic blood pressure (R2=0.090; Searle, 1971). Alternatively, by regressing change in blood pressure on change in body weight, the predicted change in blood pressure for a −0.7 kg change in weight can be estimated using the obtained coefficient (gradient) of 2.1 and 1.2 for systolic and diastolic blood pressure, respectively. The predicted change in blood pressure can then be divided by the observed change in blood pressure to give an estimate of the effect of body weight on blood pressure. In this assessment, changes in body weight accounted for approximately 27% of the change in systolic blood pressure (1.5 mm Hg × 100/5.5 mm Hg) and 33% of the change in diastolic blood pressure (0.83 mm Hg × 100/2.5 mm Hg). In this context, it is noteworthy that despite the increased fat from almonds, the diet was associated with both a reduction in body weight and blood pressure.
At 1 year, the reduction in systolic blood pressure was just over 4 mm Hg. In the recent PREMIER study, half an hour of counseling given to motivated individuals resulted in a 6.6 mm Hg reduction in systolic blood pressure 6 months later (Appel et al., 2003). Although this phenomenon has not been reported in previous studies, where weight gains rather than weight loss has been seen (Whelton, 1998), these new data indicate the value of even limited advice to motivated individuals (Appel et al., 2003).
As with the major diet and lifestyle blood pressure studies, the main effect was seen in those with the higher blood pressure (Appel et al., 1997, 2003; Sacks et al., 1999; Chobanian et al., 2003; Svetkey et al., 2005). Dividing the group into those with blood pressures above or below 130/85 mm Hg gave systolic blood pressure reductions of 13.2±1.7 versus 1.8±1.4 mm Hg, respectively. In the absence of a control group, it could be argued that the greater fall in blood pressure in those with higher starting values simply reflected regression to the mean. Nevertheless, the greater fall in those with high values is a common feature of blood pressure studies (Appel et al., 1997, 2003; Sacks et al., 1999; Chobanian et al., 2003; Svetkey et al., 2005). Age, as previously demonstrated (Svetkey et al., 2005), related positively to blood pressure reduction; however, sex appeared to be without effect. Our study was not sufficiently ethnically diverse to allow an assessment on this basis for comparison with other studies (Svetkey et al., 2005).
We conclude that a dietary portfolio approach may have particular relevance to the treatment of an increasing number of individuals in the general population who will be diagnosed with both raised blood pressure and blood lipids, as treatment targets for both blood pressure and serum lipids are progressively lowered over time. Aspects of this approach may be combined with diets, which emphasize increased consumption of plant foods, such as the low-sodium DASH diet together with weight loss and exercise advice, and with pharmacological treatment when these strategies are not enough.
This work is supported by the Canada Research Chair Endowment of the Federal Government of Canada; the Canadian Natural Sciences and Engineering Research Council of Canada; Loblaw Brands Limited; the Almond Board of California; Unilever Canada and Unilever Research & Development, Vlaardingen, The Netherlands.
We thank Ms Kathy Galbraith of Natural Temptations Bakery, Burlington, ON, Canada for her assistance on this project; and to the study participants for their attention to detail and enthusiasm.