Vegetarian Nutrition

Randomized control trial.

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To compare the cholesterol-reducing capability of a low-fat vegetarian diet containing plant sterols, viscous fibers, soy protein and almonds with a low-fat diet plus statin medication.

Healthy males and post-menopausal females with hyperlipidemia.

• Pre-menopausal females.
• The authors noted that none of the participants had a history of:
  • Cardiovascular disease
  • Untreated hypertension
  • Diabetes
  • Renal disease
  • Liver disease.

Recruitment

• Recruitment of hyperlipidemic patients at the Clinical Nutrition and Risk Factor Modification Center at St. Michael's Hospital, Toronto, Canada
• Advertisements in community newspapers.

Design

• Randomized parallel design (randomization done using a random number generator)
• Four-week intervention period
• Three groups
  • Control (C): N=16
  • Statin (S): N=14
  • Dietary Portfolio (DP): N=16.

Blinding Used

Some aspects of the study were blinded and others were not.

• Blinded
  • Patients and study personnel were blinded to type of medication
    • Participants were randomized into treatment groups by the statistician
    • Statistician held the code for the placebo and statin medication used in the study
    • Statistician was in a separate location from the study site.
  • Laboratory staff received samples labeled with participant codes and dates.
• Not blinded: Dietitians checked participants' food records.

Intervention

• Routine therapeutic low-fat diet (similar to current NCEP guidelines) for one month prior to intervention
• Participants stratified based on sex and pre-treatment LDL-C level
• Randomized into one of three treatment groups
  • Control diet plus placebo
  • Control diet plus statin
  • Dietary Portfolio diet plus placebo.
• Four-week intervention. 

Diets

• Components of the C and DP diets were balanced with respect to fatty acid profile, dietary cholesterol and fiber intake
• Diets were vegetarian but not vegan (eggs and dairy products were allowed)
• Each participant's diet was calculated to achieve weight maintenance
• All foods as well as the okra to be consumed by the participants were provided (participants picked up food at weekly clinic visits)
• Participants were instructed to purchase specific fruits and non-starchy vegetables and were reimbursed on presentation of receipts
• Seven-day rotating menu plans were used by all participants with modifications made for personal preferences as long as the overall goals for the diet were met
• Non-caloric beverages were not restricted
• Participants were given self-taring electronic scales to measure all foods both prior to and during intervention.
• Control diet was based on:
  • Skim milk, fat-free cheese and yogurt
  • Egg substitute or egg whites
  • Whole grain breakfast cereals (fiber content 2.5g per 1,000kcal)
  • Whole wheat bread (fiber content 2.0g per 1,000kcal)
  • High monounsaturated sunflower oil and safflower oil incorporated into prepared muffins to balance the fatty acid profile of the DP.
• Dietary Portfolio diet was based on:
  • Plant sterols (1.0g per 1,000kcal) via a plant sterol-enriched margarine
  • Soy protein (21.4g per 1,000kcal) using soy milk and soy meat analogs
  • Viscous fibers (9.8g per 1,000kcal)
  • Primarily from oats, barley and psyllium
  • Additionally using eggplant (0.2g per 1,000kcal) and okra (0.4g per 1,000kcal)
  • Almonds (14g per 1,000kcal)
  • Eggs (one per week) and butter (nine grams per day) were provided to balance the saturated fat and cholesterol content of C diet.

Statin Therapy

• 20mg lovastatin
  • Crushed and delivered in Veggiecap capsules
  • One capsule per day in the evening for the 28 days of the study.
• Placebo
  • Lactose and blue food coloring delivered in veggie cap capsules
  • One capsule per day in the evening for the 28 days of the study.
• All capsules were dispensed by hospital pharmacy in identical containers
• Participants returned containers for capsule counts at the end of the month.

Measurements

• Weight: Measured weekly
• Blood samples
  • 12-hour overnight fast prior to blood collection
  • Samples taken at two-week intervals.
• Blood pressure
  • Measured twice in the non-dominant arm at each clinic visit
  • Mercury sphygmomanometer used by the same observer.

Food Records

• Seven-day diet histories were recorded for the week prior to beginning the intervention
• Completed menu checklists returned weekly and checked by dietitians
• Satiety ratings were recorded weekly: Used a nine-point bipolar semantic scale
  • Minus four: Excessively hungry
  • Zero: Neutral
  • Plus four: Discomfort due to excess food intake.

Exercise

Previous week's exercise was reviewed and recorded by dietitians to ensure that it remained constant during the intervention period.

Statistical Analysis

• Change in values measured between week zero and week four:
  • Body weight
  • Blood lipids
    • Total cholesterol (TC)
    • HDL-C
    • LDL-C
    • Triglycerides.
  • Apolipoproteins A1 and B
  • Ratios
    • TC to HDL-C
    • LDL-C to HDL-C
    • Apo B to Apo A1.
  • C-reactive protein
  • Blood pressure
  • Calculated cardiovascular heart disease CHD risk.
• Differences between treatments were assessed by Student-Neuman-Keuls multiple range test
• Analysis of covariance was used to assess treatment interaction by treatment and sex
• Intention-to-treat analysis done by including the five participants for whom baseline values were available but who dropped out prior to the week two blood sample (two-tailed paired T-test used to assess the significance of the percentage change from baseline for these participants if it was assumed that they would have demonstrated either no change, 50% of the mean change or 100% of the mean change observed)
• Results reported as mean (SE)
• Significance: P<0.05.

Timing of Measurements

•  Weekly visits to clinic
  
  • Weight
  • Blood pressure
  • Menu checklists
  • Satiety ratings
  • Exercise level monitored.
• Blood samples collected at baseline, week two and week four.

Dependent Variables

• Serum lipids (mmol per L): TC, HDL-C,  LDL-C and Triglycerides
• C-reactive protein (mg per L)
• Blood pressure (mm Hg)
• Body weight (kg).

Independent Variables

• Dietary Portfolio diet: Low-fat vegetarian diet containing specific percentages of plant sterols, viscous fibers, soy protein and almonds  
• Lovastatin.

Control Variables

Most foods provided.

Initial N

55.

Attrition (Final N)

46; 25 males, 21 females.

• Four randomized participants did not start the study
• Three withdrew during first week of study (job relocation, family ill health, time commitment demands)
• Two withdrawn due to elevation of liver enzymes or muscle discomfort.

Age

59 (one) years; range, 36 years to 85 years of age.

Ethnicity

Race of Study Participants	Male	Female
European	21	20
East Indian	2	0
Chinese	1	0
Black	0	1
Hispanic	1	0

Location

Toronto, Ontario, Canada.

 

• Reductions in blood lipids and C-reactive protein in the S and DP groups were significantly greater than the respective changes in the C group
• No difference was observed in changes in blood lipids or C-reactive protein between the S and DP groups.

	Change from Baseline to Week Four			Statistical Significance Between Control and Intervention Groups*
	Control Group (C) (N=16)	Control + Statin Group (S) (N=14)	Dietary Portfolio Group (DP) (N=16)
Body Weight (kg)	-0.3 (0.2)	-0.2 (0.1)	-0.4 (0.2)	NS
Total Cholesterol (mmol per L)	-0.40 (0.11)	-1.55 (0.23)	-1.52 (0.22)	P<0.005
LDL-C (mmol per L)	-0.37 (0.09)	-1.43 (0.18) (  P<0.001)*	-1.36 (0.18) (  P=0.001)	P<0.005
HDL-C (mmol per L)	-0.12 (0.03)	-0.04 (0.04)	-0.08 (0.03)	NS
TC/HDL ratio	0.25 (0.15)	-1.24 (0.22)	-1.05 (0.24)	P<0.005
LDL/HDL ratio	0.05 (0.09)	-1.17 (0.17) (  P=0.001)	-1.03 (0.19) (  P=0.001)	P<0.005
Triglycerides (mmol per L)	0.19 (0.15)	-0.19 (0.18)	-0.19 (0.18)	NS
C-reactive Protein (mg per L)	-0.28 (0.16)	-1.50 (0.42) (  P=0.002)	-1.25 (0.62) (  P=0.02)	P<0.005
10-year CHD Risk	-0.3 (0.7)	-3.3 (0.9)	-2.9 (0.5 )	P<0.005

* Values with a   P-value indicate a significant within group change from baseline.

Comparisons of S and DP differences are statistically significant from those in C, but differences between S and DP are not significantly different from each other.

 Other Findings

• High compliance rate for all three groups:
  • C: 93% (3%)
  • S: 95% (3%)
  • DP: 94% (3%)
  • 98% of capsules provided were taken.
• Participants lost a similar amount of weight in all three groups:
  • C: 0.3 (0.2) kg, P=0.22
  • S: 0.2 (0.1) kg, P=0.15
  • DP: 0.4 (0.2) kg, P=0.06.
• No differences in response were seen between sexes
• No differences were noted between week two and week four values for LDL-C, LDL-C : HDL-C or C-reactive protein
• Calculated CHD risk was reduced similarly in the S [25.8% (4.4%)] and DP [24.9% (5.5%)] groups
• Blood lipid changes accounted for 70% and 82% of CHD risk reduction in DP and S groups, respectively.

Intake of a combination of cholesterol-lowering plant-based food components increased the effectiveness of diet as a treatment for hypercholesterolemia.

Government:	Federal Government of Canada; Canadian Natural Sciences and Engineering Research Council of Canada
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