CompletedNCT00425945Updated Apr 2, 2014Results posted

Understanding Pine Bark Extract as an Alternative Treatment (UPBEAT) Study

An interventional study of Pine Bark Extract (Flavangenol®) in Hypertension, sponsored by Stanford University. Completed at 1 site in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2014-04-02.

Sponsored by Stanford University · Not applicable, Interventional, and Prevention

Phase: Not applicable
Study type: Interventional
Enrollment: 130
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

The purpose of this study is to investigate the efficacy of Flavangenol® (Toyo Shinyaku, Japan), a pine bark extract, in lowering blood pressure and improving glycemic control and plasma lipoprotein profile.

Read the detailed description

Cardiovascular disease is the number one cause of death in the Unites States. Our study tests the efficacy of pine bark extract in improving a number of cardiovascular disease risk factors. We are conducting a randomized, placebo-controlled, double-blind, parallel trial that will investigate the efficacy and safety of Flavangenol® (Toyo Shinyaku, Japan), a pine bark extract, among 130 study participants. These participants will be individuals at mildly or moderately elevated risk of cardiovascular disease (CVD) because of having prehypertension, excess body weight, and insulin insensitivity. We aim to determine (in order of priority):

The efficacy of Flavangenol in lowering blood pressure.
The efficacy of Flavangenol in improving glycemic control and plasma lipoprotein profile.
Changes in body weight, antioxidative capacity, anti-inflammatory markers, blood coagulation factors, and liver function tests in response to Flavangenol.
The safety of Flavangenol, as confirmation of past studies.

Conditions studied

Hypertension

Browse trials for

Hypertension 6,834

In context

Hypertension

6,834 studies on the registry are indexed under Hypertension; 971 are open to participants now.

This study's enrollment of 130 is above the median of 90 across 5,095 interventional studies indexed under Hypertension.

Browse Hypertension studies →

Lead sponsor

Stanford University is the lead sponsor of 2,161 studies on the registry; 428 are open to participants now.

Of its 268 completed or terminated interventional studies of FDA-regulated products, 207 (77%) have results posted.

Browse Stanford University studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Systolic blood pressure between 125 and 159 mmHg and diastolic blood pressure (DBP) \< 100 mmHg
Body mass index (BMI) 25.0-34.9
Triglycerides (TG) \< 450 mg/dL
Low Density Lipoprotein (LDL) \< 200 mg/dL
Fasting blood glucose (FBG) \< 126 mg/dL

Exclusion criteria

Exclusion Criteria:

DBP > 95 mmHg
LDL > 170 mg/dL
TG > 300 mg/dL
FBG > 110 mg/dL

Study design

Phase: Not applicable
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Investigator, Outcomes assessor)
Enrollment: 130 participants (actual)

Study arms

Placebo comparator
Placebo
Placebo delivered as four tablets matching the active product once daily orally.
Drug: Pine Bark Extract (Flavangenol®)
Active comparator
Pine Bark Extract
Flavangenol 200 mg Flavangenol is a brand of Pine Bark Extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, each containing 50 mg Flavangenol, all 4 tablets taken once per day.
Drug: Pine Bark Extract (Flavangenol®)

Interventions

DrugPine Bark Extract (Flavangenol®)
Flavangenol 200 mg per day. Flavangenol is a brand of pine bark extract manufactured by Toyo Shinyaku of Saga, Japan. Dosage delivered as four tablets, each containing 50 mg Flavangenol, all 4 tablets taken once per day orally for 12 weeks.
Also known as: Pycnogenol (differing formulation)

What researchers measure

Primary outcomes

Combined Change in Systolic and Diastolic Blood Pressures From Baseline to Week 12.
Mean at Week 12 observation minus mean at Baseline observation.
Time frame: three months

Secondary outcomes

Total Cholesterol
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: 3 months
LDL
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: 3 months
HDL
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: 3 months
Triglycerides
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months
LDL Particle Size
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: 3 months
HDL Particle Size
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: 3 months
Lipoprotein A
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). Calculated as (Pinebark\_Followup - Pinebark\_Baseline) - (Placebo\_Follow-up - Placebo\_Baseline)
Time frame: three months
C-reactive Protein
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months
Body Mass Index
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months
Weight
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: 3 months
Fasting Blood Glucose
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months
Fasting Insulin
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months
Hemoglobin A1c
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months
ALT/SGPT
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months
AST/SGOT
Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).
Time frame: three months

Results

Posted Apr 2, 2014

Participant flow

Participants were recruited from the local community through the use of radio and print advertisements between January 31, 2007 and May 31, 2008.

Participant flow — Overall Study
Milestone	Pine Bark Extract	Placebo
Started	64	66
Completed	60	61
Not completed	4	5
Withdrew: Concern about supplement	2	0
Withdrew: Inconvenience	0	2
Withdrew: Lost to follow-up	0	2
Withdrew: Began hypertension medication	1	0
Withdrew: Began cancer treatments	1	0
Withdrew: Moved from area	0	1

Outcome measures

PrimaryCombined Change in Systolic and Diastolic Blood Pressures From Baseline to Week 12.

Mean at Week 12 observation minus mean at Baseline observation.

Time frame:: three months
Reported as:: Mean · mm Hg

Combined Change in Systolic and Diastolic Blood Pressures From Baseline to Week 12.
mm Hg	Pine Bark Extract	Placebo
Combined Change in Systolic and Diastolic Blood Pressures From Baseline to Week 12.	-1.0 (-4.2 to 2.1)	-1.9 (-5.5 to 1.7)

SecondaryTotal Cholesterol

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Time frame:: 3 months
Reported as:: Mean · mg/dL

Total Cholesterol
mg/dL	Pine Bark Extract (Net Change)	Placebo (Net Change)
Total Cholesterol	5.4 ± 17.5	-2.0 ± 23.7

Statistical analysis

Pine Bark Extract (Net Change) vs Placebo (Net Change) · Mean difference (net): 7.3 · 95% CI -0.1 to 14.9

SecondaryLDL

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Time frame:: 3 months
Reported as:: Mean · mg/dL

LDL
mg/dL	Pine Bark Extract (Net Change)	Placebo (Net Change)
LDL	3.3 ± 16.6	-1.1 ± 19.7

Statistical analysis

Pine Bark Extract (Net Change) vs Placebo (Net Change) · Mean difference (net): 4.4 · 95% CI -2.1 to 10.8

SecondaryHDL

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Time frame:: 3 months
Reported as:: Mean · mg/dL

HDL
mg/dL	Pine Bark Extract (Net Change)	Placebo (Net Change)
HDL	-0.9 ± 6.0	-1.3 ± 5.6

Statistical analysis

Pine Bark Extract (Net Change) vs Placebo (Net Change) · Mean difference (net): 0.4 · 95% CI -1.7 to 2.5

SecondaryTriglycerides

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Time frame:: three months
Reported as:: Mean · mg/dL

Triglycerides
mg/dL	Pine Bark Extract (Net Change)	Placebo (Net Change)
Triglycerides	17.2 ± 50.6	-1.0 ± 63.0

Statistical analysis

Pine Bark Extract (Net Change) vs Placebo (Net Change) · Mean difference (net): 18.2 · 95% CI -2.3 to 38.7

SecondaryLDL Particle Size

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Time frame:: 3 months
Reported as:: Mean · nm

LDL Particle Size
nm	Pine Bark Extract (Net Change)	Placebo (Net Change)
LDL Particle Size	31.4 ± 200.2	28.5 ± 248.5

Statistical analysis

Pine Bark Extract (Net Change) vs Placebo (Net Change) · Mean difference (net): 0.1 · 95% CI -0.1 to 0.3

SecondaryHDL Particle Size

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Time frame:: 3 months
Reported as:: Mean · nm

HDL Particle Size
nm	Pine Bark Extract (Net Change)	Placebo (Net Change)
HDL Particle Size	1.0 ± 3.1	0.0 ± 4.2

Statistical analysis

Pine Bark Extract (Net Change) vs Placebo (Net Change) · Mean difference (net): 0.0 · 95% CI -0.0 to 0.1

SecondaryLipoprotein A

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up). Calculated as (Pinebark\_Followup - Pinebark\_Baseline) - (Placebo\_Follow-up - Placebo\_Baseline)

Time frame:: three months
Reported as:: Mean · nmol/L

Lipoprotein A
nmol/L	Pine Bark Extract (Net Change)	Placebo (Net Change)
Lipoprotein A	-1.3 ± 10.3	1.8 ± 10.0

Statistical analysis

Pine Bark Extract (Net Change) vs Placebo (Net Change) · Mean difference (net): -3.2 · 95% CI -6.8 to 0.5

SecondaryC-reactive Protein

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Time frame:: three months
Reported as:: Mean · nmol/L

C-reactive Protein
nmol/L	Pine Bark Extract (Net Change)	Placebo (Net Change)
C-reactive Protein	-0.2 ± 2.56	0.3 ± 2.9

Statistical analysis

Pine Bark Extract (Net Change) vs Placebo (Net Change) · Mean difference (net): -0.5 · 95% CI -1.5 to 0.5

SecondaryBody Mass Index

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Time frame:: three months
Reported as:: Mean · kg/m^2

Body Mass Index
kg/m^2	Pine Bark Extract (Net Change)	Placebo (Net Change)
Body Mass Index	0.1 ± 0.4	-0.1 ± 0.6

Statistical analysis

Pine Bark Extract (Net Change) vs Placebo (Net Change) · Mean difference (net): 0.2 · 95% CI 0.0 to 0.4

SecondaryWeight

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Time frame:: 3 months
Reported as:: Mean · lb

Weight
lb	Pine Bark Extract (Net Change)	Placebo (Net Change)
Weight	0.6 ± 3.1	-0.6 ± 3.4

Statistical analysis

Pine Bark Extract (Net Change) vs Placebo (Net Change) · Mean difference (net): 1.2 · 95% CI 0.1 to 2.4

SecondaryFasting Blood Glucose

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Time frame:: three months
Reported as:: Mean · mg/dL

Fasting Blood Glucose
mg/dL	Pine Bark Extract (Net Change)	Placebo (Net Change)
Fasting Blood Glucose	-1.0 ± 9.8	0.1 ± 8.7

Statistical analysis

Pine Bark Extract (Net Change) vs Placebo (Net Change) · Mean difference (net): -1.0 · 95% CI -4.4 to 2.3

SecondaryFasting Insulin

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Time frame:: three months
Reported as:: Mean · mg/dL

Fasting Insulin
mg/dL	Pine Bark Extract (Net Change)	Placebo (Net Change)
Fasting Insulin	0.2 ± 4.2	-0.6 ± 5.2

Statistical analysis

Pine Bark Extract (Net Change) vs Placebo (Net Change) · Mean difference (net): 0.8 · 95% CI -0.9 to 2.5

SecondaryHemoglobin A1c

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Time frame:: three months
Reported as:: Mean · mg/dL

Hemoglobin A1c
mg/dL	Pine Bark Extract (Net Change)	Placebo (Net Change)
Hemoglobin A1c	-0.0 ± 0.2	-0.0 ± 0.2

Statistical analysis

Pine Bark Extract (Net Change) vs Placebo (Net Change) · Mean difference (net): 0.0 · 95% CI -0.1 to 0.1

SecondaryALT/SGPT

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Time frame:: three months
Reported as:: Mean · u/L

ALT/SGPT
u/L	Pine Bark Extract (Net Change)	Placebo (Net Change)
ALT/SGPT	0.8 ± 15.11	-3.0 ± 15.28

Statistical analysis

Pine Bark Extract (Net Change) vs Placebo (Net Change) · Mean difference (net): 3.8 · 95% CI -1.6 to 9.3

SecondaryAST/SGOT

Net change in secondary outcomes from Baseline to 12 Weeks (Follow-up).

Time frame:: three months
Reported as:: Mean · u/L

AST/SGOT
u/L	Pine Bark Extract (Net Change)	Placebo (Net Change)
AST/SGOT	0.2 ± 4.9	1.4 ± 6.8

Statistical analysis

Pine Bark Extract (Net Change) vs Placebo (Net Change) · Mean difference (net): -1.3 · 95% CI -3.4 to 0.8

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Pine Bark Extract	—	1/64 (1.6%)	24/64 (37.5%)
Placebo	—	2/66 (3%)	29/66 (43.9%)

Most frequent serious events

Most frequent serious events
Event	Pine Bark Extract	Placebo
Emergency DepartmentMusculoskeletal and connective tissue disorders	0/64	2/66
HospitalizedSurgical and medical procedures	1/64	0/66

Most frequent other events

Most frequent other events
Event	Pine Bark Extract	Placebo
Headache (week 12)Nervous system disorders	8/64	13/66
Gastrointestinal Discomfort (week 3)Gastrointestinal disorders	12/64	9/66
Sleepiness (week 12)General disorders	5/64	12/66
Insomnia (week 6)Nervous system disorders	4/64	11/66
Gastrointestinal Discomfort (week 6)Gastrointestinal disorders	8/64	3/66
Other (week 6)General disorders	7/64	2/66
Dizziness (week 12)Nervous system disorders	3/64	7/66
Nause (week 12)Gastrointestinal disorders	6/64	1/66
Increased Perspiration (week 6)General disorders	5/64	1/66
Dizziness (week 3)Nervous system disorders	1/64	5/66

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Pine Bark Extract	Placebo	Total
<=18 years	0	0	0
Between 18 and 65 years	51	55	106
>=65 years	13	11	24

Age, Continuous
Age, Continuous(years)	Pine Bark Extract	Placebo	Total
Mean	56.9 ± 9.8	53.9 ± 12.0	55.4 ± 11.0

Sex: Female, Male
Sex: Female, Male(Participants)	Pine Bark Extract	Placebo	Total
Female	25	23	48
Male	39	43	82

Study locations

1 site

Stanford University School of Medicine
Stanford, California 94305, United States

References and documents

Publications

Drieling RL, Gardner CD, Ma J, Ahn DK, Stafford RS. No beneficial effects of pine bark extract on cardiovascular disease risk factors. Arch Intern Med. 2010 Sep 27;170(17):1541-7. doi: 10.1001/archinternmed.2010.310. PubMed 20876405 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 2, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00425945
Lead sponsor: Stanford University
Collaborators: Funded by Toyo Shinyaku Co Ltd
Responsible party: Randall Stafford (Professor of Medicine, Stanford University) — Principal investigator
First posted: Jan 24, 2007
Start date: Oct 2006
Primary completion: Aug 2008
Completion: Aug 2008
Results posted: Apr 2, 2014
Last update: Apr 2, 2014

Study contacts

Randall S. Stafford MD, PhD

principal investigator · Stanford University

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2014. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Pycnogenols

Other studies in this condition

Hypertension →

Other studies from this sponsor

Stanford University →

Start the discussion

Understanding Pine Bark Extract as an Alternative Treatment (UPBEAT) Study

Study summary

Conditions studied

Browse trials for

In context

Hypertension

Lead sponsor

Who can participate

✓Inclusion criteria

✕Exclusion criteria

Study design

Study arms

Interventions

What researchers measure

Primary outcomes

Secondary outcomes

Results

Participant flow

Outcome measures

Adverse events

Baseline characteristics

Study locations

References and documents

Publications

Updates

Registry details

Key details

Study contacts

Oversight

Not currently enrolling

Follow this study

Discussion

Other studies in this condition

Other studies from this sponsor

Inclusion criteria

Exclusion criteria