Bromelain and Cardiovascular Risk Factors in Diabetes (BRCARDIO)

The purpose of the study is to evaluate the effect of dietary supplementation of bromelain (a proteolytic enzyme from the pineapple plant) on the reduction of plasma fibrinogen level among type 2 diabetic subjects who have a high risk of cardiovascular disease.

The null hypothesis [Ho] is: there is no significant improvement in plasma fibrinogen, serum lipid profile, blood pressure, BMI, waist circumference and C-reactive protein for subjects with type 2 diabetes who are at risk of CVD following the intervention of bromelain supplementation compared to placebo group.

The alternative hypothesis [H1] is: there is a significant improvement in plasma fibrinogen, serum lipid profile, blood pressure, BMI, waist circumference and C-reactive protein for subjects with type 2 diabetes who are at risk of CVD following the intervention of bromelain supplementation compared to placebo group.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease.
• Intervention / Treatment: Dietary supplement: placebo (wheat starch); Dietary supplement: bromelain capsule

Detailed Description

According to American Heart Association (2010), heart disease and stroke are the No. 1 causes of death and disability among people with type 2 diabetes. At least 65% of people with diabetes die from some form of heart disease or stroke. Type 2 diabetes is associated with a two to fourfold increased incidence of ischemic cardiovascular events and markedly enhances the risk of stroke(Coutinho et al, 1999) due to a variety of associated risk factors that include high blood pressure, lipid disorders, high low-density lipoproteins (LDL) cholesterol, high triglycerides, low high-density lipoproteins (HDL) cholesterol, smoking, obesity, lack of physical activity and poorly controlled blood sugars(American Heart Association 2010).

Bromelain, a crude extract from the pineapple plant, was first introduced as a therapeutic compound in 1957 (Heinicke & Gortner, 1957). Heinicke et al. (1971) reported that bromelain was effective for use in cardiovascular diseases as an inhibitor of blood platelet aggregation, minimizing the risk of arterial thrombosis and embolism.

A literature review identified only three human studies (in Honolulu and Germany). In view of this review and the valuable therapeutic properties of bromelain to cardiovascular disease, there is a need for a study to confirm bromelain's use for cardiovasular disease.

This study is a randomized placebo control, parallel design, and double blind, pilot efficacy study which was carried out in Hebei Yiling Hospital, China. The study assessed the effects of 12 weeks of bromelain (1050mg/day) supplementation on plasma fibrinogen level compared to usual care. Study participants were type 2 diabetes who have a risk of developing cardiovascular disease.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Shijiazhuang, Beijing, China, 050091
      • Hebei Yiling Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age over 18 years old

• Diagnosed type 2 diabetes (HbA1C at >6,5%), who are at a risk of CVD indicated with the following risk parameters:

  • total cholesterol between 5.0 - 6.2 mmol/l (195.0 - 241.8 mg/dL),
  • Body Mass Index (BMI) > 25 kg/m2
  • Waist circumference > 101.6 cm (40 inches) for men and > 88.9 cm (35 inches) for women
  • Triglycerides > 1.7 mmol/L (150mg/dL)
  • HDL-cholesterol < 1 mmol/L (40 mg/dL) for men, < 1.3 mmol/L (50 mg/dL) for women
  • LDL-cholesterol > 2.6 mmol/L (100 mg/dL)
  • Blood pressure > 140/90mm Hg

Exclusion Criteria:

• Pregnant or trying to become pregnant or lactating women
• Subjects unwilling or unable to comply with study procedure
• Subjects with severe health problems including renal disease, liver disease, cardiovascular disease, and other chronic ill health conditions.
• Subjects on drug cardiovascular medication like warfarin, aspirin.
• Subjects that are taking statins.
• Subjects taking bromelain supplement and other herbal supplements known to be effective e.g. cinnamon.
• Subjects have a history of allergic reactions to bee stings, olive tree pollen or pineapple.
• Subjects have a history of occupational inhalant/skin contact with bromelain.
• Subjects have diabetes ketoacidosis recently (past 2 weeks).
• Unable to provide informed consent i.e. unable to follow diet control advice or not willing to follow study procedure.
• Subjects who is on any Chinese herbs medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo group; This group will receive placebo capsule (wheat starch) for 12 weeks period. The 1050 mg dosage of wheat starch was divided into three capsules and to be taken two (2 x 350 mg) after breakfast and another one (350 mg) after dinner. The capsules should be taken two hours after the meals.	Dietary supplement: placebo (wheat starch); Placebo group received placebo capsule (wheat starch) for 12 weeks period. The 1050 mg dosage of wheat starch was divided into three capsules and to be taken two (2 x 350 mg) after breakfast and another one (350 mg) after dinner. The capsules should be taken two hours after the meals.
Active Comparator: bromelain group; Bromelain Group This group will receive bromelain capsule for 12 weeks period. The 1050 mg dosage of bromelain was divided into three capsules and to be taken two (2 x 350 mg) after breakfast and another one (350 mg) after dinner. The capsules should be taken two hours after the meals.	Dietary supplement: bromelain capsule; Bromelain group received bromelain capsule for 12 weeks period. The 1050 mg dosage of bromelain was divided into three capsules and to be taken two (2 x 350 mg) after breakfast and another one (350 mg) after dinner. The capsules should be taken two hours after the meals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fibrinogen	This study is to assess the effects of 12 weeks of bromelain (1050mg/day) supplementation on plasma fibrinogen level compared to usual care.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum lipid profile (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides)	This study is to assess the effects of 12 weeks of bromelain (1050mg/day) supplementation on changes of serum lipid profile compared to usual care.	12 weeks
HbA1c	This study is to assess the effects of 12 weeks of bromelain (1050mg/day) supplementation on changes of HbA1c compared to usual care.	12 weeks
C-reactive protein	This study is to assess the effects of 12 weeks of bromelain (1050mg/day) supplementation on changes of C-reactive protein compared to usual care.	12 weeks
Body Mass Index	This study is to assess the effects of 12 weeks of bromelain (1050mg/day) supplementation on changes of body mass index compared to usual care.	12 weeks
Blood pressure	This study is to assess the effects of 12 weeks of bromelain (1050mg/day) supplementation on changes of blood pressure compared to usual care.	12 weeks
Alanine transaminase	This study is to assess the effect of 12 weeks of bromelain (1050mg/day) supplementation on changes of alanine transaminase (for liver function test) compared to usual care.	12 weeks
Aspartate aminotransferase	This study is to assess the effect of 12 weeks of bromelain (1050mg/day) supplementation on changes of aspartate aminotransferase(for liver function test) compared to usual care.	12 weeks
blood urea nitrogen	This study is to assess the changes of 12 weeks of bromelain (1050mg/day) supplementation on blood urea nitrogen(for kidney function test) compared to usual care.	12 weeks
Creatinine	This study is to assess the effect of 12 weeks of bromelain (1050mg/day) supplementation on changes of creatinine(for kidney function test) compared to usual care.	12 weeks

Collaborators and Investigators

• Sponsor: Hebei Yiling Hospital
• Collaborators: London South Bank University
• Investigators: Principal Investigator: Ley C M, Ms, London South Bank University

Publications and helpful links

General Publications

• American Heart Association. Prevention, Secondary. 2010. Available online at www.americanheart.org/print_presenter.jhtml [assessed 17th April 2010]
• Heinicke, R.M. & Gortner, W.A. 1957. Stem Bromelain - A New Protease Preparation from Pineapple Plants. Economic Botany, 11, 225-234
• Heinicke RM, van der Wal L, Yokoyama M. Effect of bromelain (Ananase) on human platelet aggregation. Experientia. 1972 Jul 15;28(7):844-5. doi: 10.1007/BF01923166. No abstract available.
• Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care. 1999 Feb;22(2):233-40. doi: 10.2337/diacare.22.2.233.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: January 30, 2012
• First Submitted That Met QC Criteria: January 30, 2012
• First Posted (Estimate): February 1, 2012

Study Record Updates

• Last Update Posted (Estimate): September 24, 2012
• Last Update Submitted That Met QC Criteria: September 20, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: cardiovascular disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: BR2012