Flaxseed Lignan Supplementation in Elderly Participants With Stage I Hypertension

Flaxseed Lignan Enriched Complex for Blood Pressure Reduction in Elderly Participants With High Normal Blood Pressure or Stage I Hypertension

Current recommendations today suggest that use of therapeutic lifestyle changes, such as supplementation with specific dietary components and moderate exercise, are appropriate interventions for individuals with borderline high blood pressure. Dietary intervention with natural products, such as flaxseed, is associated with decreased prevalence of cardiovascular disease (Adolphe 2010). Lignans are the active compounds in flaxseed believed to mediate the cardiovascular health benefits following flaxseed consumption (Peterson 2010). Clinical trials indicate benefit of Flax Lignan Enriched Complex (FLC) (BeneFlax® from Archer Daniels Midland, a natural product derived from flaxseed composed of 34-38% lignan) for reducing blood cholesterol and glucose (Pan 2007; Zhang 2008) and blood pressure (Cornish 2009). Furthermore, a recent study in atherosclerosis patients showed significant clinical benefit of flaxseed meal for reducing blood pressure (Rodriguez-Leyva 2013). As a therapeutic lifestyle change that could prevent a need to introduce drug therapy in elderly patients, the effectiveness of FLC supplementation alone or in combination with moderate exercise merits investigation.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Dietary supplement: BeneFlax®; Behavioral: Walking training; Behavioral: Dash Eating Plan; Dietary supplement: Placebo (Whey Protein); Behavioral: Flexibility training

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 5E5
      • College of Pharmacy, University of Saskatchewan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• High normal blood pressure (130/85 - 139/89) or stage I hypertension (140/90 - 150/90)
• Ability to follow simple instructions

Exclusion Criteria:

• Age below 60 years.
• Individuals living in long term care homes.
• Individuals unable to walk for 30 minutes.
• Unstable diabetes, or diabetics taking insulin (note: eligible diabetic participants will undergo additional testing during the study ).
• Current cancer or diagnosed with cancer in the past 2 years.
• Significant liver or other gastrointestinal disorder including inflammatory bowel disease. (While constipation is the most common gastrointestinal problem in the elderly, it would not be a contraindication)
• Significant kidney disorder.
• Have taken oral antibiotics in the past three months
• Unstable or severe cardiac disease, recent myocardial infarction, or stroke (either in past 6 months or significantly affecting physical mobility).
• Unstable other medical disease including, but not limited to, pulmonary disorder, epilepsy and genitourinary disorder.
• Migraine with aura within the last year (as this is a risk factor for stroke).
• Current diagnosis of a bleeding condition, or at risk of bleeding.
• Significant immune-compromise.
• Current use of hormone replacement therapy (except thyroid).
• Current use of blood pressure medications and/or diuretics
• Current use of flax seed supplement
• Participation in any other clinical trial with an investigational agent within one month prior to randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BeneFlax® + walking training (Dash); BeneFlax (0.8 g, twice a day) with exercise training (30-60 minutes walking training, 5 times a week) for 8 weeks; all participants encouraged to follow Dash Eating Plan.	Dietary supplement: BeneFlax®; Daily ingestion of 600 mg SDG/day in 1.6 g SDG-enhanced flax lignan (BeneFlax®) with walking training or flexibility training; Other Names: Flaxseed lignan enriched complex; Behavioral: Walking training; 30-60 minutes walking training, 5 days/week.; Behavioral: Dash Eating Plan; Dietary Approaches to Stop Hypertension (DASH), a balanced eating plan - all participants in all treatment arms will be encouraged to adopt a DASH eating plan.
Placebo Comparator: Placebo + walking training (Dash); Placebo (whey powder isocaloric to BeneFlax) with exercise training (30-60 minutes walking training, 5 times a week) for 8 weeks; all participants encouraged to follow Dash Eating Plan.	Behavioral: Walking training; 30-60 minutes walking training, 5 days/week.; Behavioral: Dash Eating Plan; Dietary Approaches to Stop Hypertension (DASH), a balanced eating plan - all participants in all treatment arms will be encouraged to adopt a DASH eating plan.; Dietary supplement: Placebo (Whey Protein); 0.6 g/day (an amount equal in volume to BeneFlax®) with walking training or flexibility training
Experimental: BeneFlax® + flexibility training (Dash); BeneFlax (0.8 g, twice a day) with placebo exercise training (flexibility training, 5 times a week) for 8 weeks; all participants encouraged to follow Dash Eating Plan.	Dietary supplement: BeneFlax®; Daily ingestion of 600 mg SDG/day in 1.6 g SDG-enhanced flax lignan (BeneFlax®) with walking training or flexibility training; Other Names: Flaxseed lignan enriched complex; Behavioral: Dash Eating Plan; Dietary Approaches to Stop Hypertension (DASH), a balanced eating plan - all participants in all treatment arms will be encouraged to adopt a DASH eating plan.; Behavioral: Flexibility training; 5 days/week; e.g. stretching training at home
Sham Comparator: Placebo + flexibility training (Dash); Placebo (whey powder isocaloric to BeneFlax) with placebo exercise training (flexibility training, 5 times a week) for 8 weeks; all participants encouraged to follow Dash Eating Plan.	Behavioral: Walking training; 30-60 minutes walking training, 5 days/week.; Behavioral: Dash Eating Plan; Dietary Approaches to Stop Hypertension (DASH), a balanced eating plan - all participants in all treatment arms will be encouraged to adopt a DASH eating plan.; Behavioral: Flexibility training; 5 days/week; e.g. stretching training at home

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 24 h ambulatory systolic blood pressure	Reduction in 24 h ambulatory systolic blood pressure at midpoint (week 4) and end (week 8) of the intervention relative to baseline value is the primary outcome of the intervention.	Baseline, week 4, and week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body weight	Change in body weight at midpoint (week 4) and end (week 8) of the intervention relative to baseline value.	Baseline, week 4, and week 8
Heart rate		Baseline
Glucometer fasting blood glucose	Diabetes only; Blood glucose monitored to ensure intervention does not result in hypoglycemia.	Baseline
Change in blood markers of safety and cardiovascular disease risk factors (clinical biochemical panel including fasting glucose, lipids, cholesterol, electrolytes, C-reactive protein)	These parameters will be measured individual but reviewed as a composite to confirm safety and any change in cardiovascular disease risk.	Baseline, week 4, and week 8
Blood levels of the flax lignan, secoisolariciresinol diglucoside (SDG), and its metabolites		Week 4
Physical activity assessment tool (PASE)		Baseline
Block Food Frequency Questionnaire		Baseline
Change in Body composition by DXA (Dual-energy X-ray absorptiometry)	Change in body composition at midpoint (week 4) and end (week 8) of the intervention relative to baseline value.	Baseline, week 4, and week 8
Heart Rate		week 4
Heart Rate		Week 8
Change in lying and standing blood pressure	Change in lying and standing blood pressure at midpoint (week 4) and end (week 8) of the intervention relative to baseline value.	Baseline, week 4, and week 8
Respiratory rate		Baseline
Respiratory rate		Week 4
Respiratory rate		Week 8
Block Food Frequency Questionnaire		Week 8
Blood levels of the flax lignan, secoisolariciresinol diglucoside (SDG), and its metabolites		Week 8
Glucometer fasting blood glucose	Diabetes only; Blood glucose monitored to ensure intervention does not result in hypoglycemia.	Week 4
Glucometer fasting blood glucose	Diabetes only; Blood glucose monitored to ensure intervention does not result in hypoglycemia.	Week 8

Other Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events as a safety measurement	Continuously throughout 9 weeks
Number of participants with severe non-compliance with the protocol	Continuously throughout 9 weeks

Collaborators and Investigators

• Sponsor: University of Saskatchewan

Publications and helpful links

General Publications

• Peterson J, Dwyer J, Adlercreutz H, Scalbert A, Jacques P, McCullough ML. Dietary lignans: physiology and potential for cardiovascular disease risk reduction. Nutr Rev. 2010 Oct;68(10):571-603. doi: 10.1111/j.1753-4887.2010.00319.x.
• Pan A, Sun J, Chen Y, Ye X, Li H, Yu Z, Wang Y, Gu W, Zhang X, Chen X, Demark-Wahnefried W, Liu Y, Lin X. Effects of a flaxseed-derived lignan supplement in type 2 diabetic patients: a randomized, double-blind, cross-over trial. PLoS One. 2007 Nov 7;2(11):e1148. doi: 10.1371/journal.pone.0001148.
• Zhang W, Wang X, Liu Y, Tian H, Flickinger B, Empie MW, Sun SZ. Dietary flaxseed lignan extract lowers plasma cholesterol and glucose concentrations in hypercholesterolaemic subjects. Br J Nutr. 2008 Jun;99(6):1301-9. doi: 10.1017/S0007114507871649. Epub 2007 Dec 6.
• Cornish SM, Chilibeck PD, Paus-Jennsen L, Biem HJ, Khozani T, Senanayake V, Vatanparast H, Little JP, Whiting SJ, Pahwa P. A randomized controlled trial of the effects of flaxseed lignan complex on metabolic syndrome composite score and bone mineral in older adults. Appl Physiol Nutr Metab. 2009 Apr;34(2):89-98. doi: 10.1139/H08-142.
• Rodriguez-Leyva D, Weighell W, Edel AL, LaVallee R, Dibrov E, Pinneker R, Maddaford TG, Ramjiawan B, Aliani M, Guzman R, Pierce GN. Potent antihypertensive action of dietary flaxseed in hypertensive patients. Hypertension. 2013 Dec;62(6):1081-9. doi: 10.1161/HYPERTENSIONAHA.113.02094. Epub 2013 Oct 14.
• Adolphe JL, Whiting SJ, Juurlink BH, Thorpe LU, Alcorn J. Health effects with consumption of the flax lignan secoisolariciresinol diglucoside. Br J Nutr. 2010 Apr;103(7):929-38. doi: 10.1017/S0007114509992753. Epub 2009 Dec 15.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: February 28, 2015
• First Submitted That Met QC Criteria: March 12, 2015
• First Posted (Estimate): March 18, 2015

Study Record Updates

• Last Update Posted (Actual): January 10, 2018
• Last Update Submitted That Met QC Criteria: January 8, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: High normal blood pressure; Stage I
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: FSL132

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No