Cost Versus Benefit of Plant Extracts Cost Versus Benefit of Plant Extracts (Pycnogenol(Pycnogenol®®) in Diabetes Risk ) in Diabetes Risk

ReductionReduction

PycnogenolPycnogenol

Standardized extract from bark of French maritime pine (Pinus maritima)

Primarily comprises of Phenolic compounds (catechin, epicatechin, and

taxifolin) Flavonoids (procyanidins and proanthocyanidins)

Mediates a number of beneficial effects in the cardiovascular system

Hypertension, diabetes, dyslipidemia Improvement of endothelial function and NO

production

Bioflavonoids (PycnogenolBioflavonoids (Pycnogenol®®))in Reduction of Hypertensionin Reduction of HypertensionDuring Treatment of DiabeticsDuring Treatment of Diabetics

to Minimize use of to Minimize use of Pharmaceutical DrugsPharmaceutical Drugs

glucose transportis impaired

glucose transportis impaired

glucosetransporter

glucosetransporter

body cellbody cell

bloo

d su

gar

leve

l [m

g/dl

]

50

100

150

200

250

bloo

d su

gar

leve

l [m

g/dl

]

50

100

150

200

250

48 type II diabetes patients (40-75 years)double-blind, placebo controlled, 12 weeks treatment

They are on medication: sulfonylurea, metformin, glitazonesbut fasting blood is still high: >140 mg/dL (120 is healthy)

Patients are medicated with ACE-inihibtorsBut patients remain borderline hypertensive(average baseline systolic blood pressure 137 mmHg)

48 type II diabetes patients (40-75 years)double-blind, placebo controlled, 12 weeks treatment

They are on medication: sulfonylurea, metformin, glitazonesbut fasting blood is still high: >140 mg/dL (120 is healthy)

Patients are medicated with ACE-inihibtorsBut patients remain borderline hypertensive(average baseline systolic blood pressure 137 mmHg)Zibadi et al., Nutr Res 28: 315-320, 2008

O

OH

OH

OHOH

OH

O

OH

OH

OHOH

OH

O

OH

OH

OHOH

OH

O

OH

OH

OHOH

OH

OHOH

O

OH

OH

OH

OHOH

O

OH

OH

OH

ConstituentsConstituents

Procyanidins:linked catechin

subunits

Procyanidins:linked catechin

subunits

Composition defined in:United States

Pharmacopoeia (28)

Composition defined in:United States

Pharmacopoeia (28)

α-glucosidase disassembles starch

PycnogenolPycnogenol®® inhibits inhibits αα-glucosidase-glucosidase

Schäfer et al., Diab Res Clin Prac 77: 41-46, 2007

Schäfer et al., Diab Res Clin Prac 77: 41-46, 2007

PycnogenolPycnogenol®® slows sugar absorption slows sugar absorptionand prolongs satietyand prolongs satiety

3 weeks200 mg a day

3 weeks100 mg a day

3 weeks50 mg a day

Blood glucose after mealsBlood glucose after meals

Fasting blood glucose in the morningFasting blood glucose in the morning

-3.3%-4.7%

-5.3%

Liu et al., Diabetes Care 27: 839, 2004

Zibadi et al., Nutr Res 28: 315-320, 2008

start 1 month 2 months 3 months

HbA1c %

-0.8

-0.6

-0.4

-0.2

0 1 2 3 4

Zibadi et al., Nutr Res 28: 315-320, 2008

Zibadi et al., Nutr Res 28: 315-320, 2008

-4

-3

-2

-1

0 1 2 3 4

start 1 month 2 months 3 months

PlasmaEndothelin-1pg/ml

Zibadi et al., Nutr Res 28: 315-320, 2008

Zibadi et al., Nutr Res 28: 315-320, 2008

Zibadi et al., Nutr Res 28: 315-320, 2008

start 1 month 2 months 3 monthsSerum LDL

mg/dL

-14-12-10-8-6-4-2024

1 2 3 4

Zibadi et al., Nutr Res 28: 315-320, 2008

start 1 month 2 months 3 months

Urinaryalbuminmg/L

-12-10-8-6-4-20246

1 2 3 4

Zibadi et al., Nutr Res 28: 315-320, 2008

Comparison of risk-factor reduction with Comparison of risk-factor reduction with cardiovascular risk-reducing drugs versus Pycnogenol cardiovascular risk-reducing drugs versus Pycnogenol

Improvement in:

Pycnogenol Ramipril(10-5 mg

daily)

Pravastatin(10-20 mg

daily)

Nifedipine (10 mg daily)

Aspirin(500 mg

daily)

Systolic BP

Mean total cholesterol

LDL-cholesterol

Serum endothelin-1

Platelet Reactivity

5% Decrease 200 mg

daily

7.9% 120 mg daily

19.2% 120 mg daily

20% 100 mg daily

12.7% 125 mg daily

50% Dose reduction

-

-

-

-

-

11.5%

18.0%

-

-

-

-

-

50% dose reduction

-

-

-

-

-

0.75%

Cost comparison of cardiovascular Cost comparison of cardiovascular risk-reducing drugs with Pycnogenolrisk-reducing drugs with Pycnogenol

Drug Dose (mg) Cost per Pill Yearly Cost

Pycnogenol

Ramipril

Pravastatin

Nifedipine

Aspirin

100200

10

40

20

325

$0.61$0.39

$1.67

$1.67

$2.50

$0.01

$223$142

$608

$608

$913

$4.85

Side effects for diabetes treatmentsSide effects for diabetes treatments

Pycnogenol Metformin Glipizide Repaglinide

Side effect prevalence

Side effect description

Minimal

Dizziness, nausea

Common

Abdominal pain, diarrhea

Minimal

Hypoglycemia

Minimal

Hypoglycemia

Cost-effectiveness of pycnogenol and Cost-effectiveness of pycnogenol and traditional treatments for type II diabetestraditional treatments for type II diabetes

Pycnogenol(125 mg/day)

Metformin(2,000 mg/day)

Glipizide(20 mg/day)

Repaglinide(2 mg/day)

Improvement in:

HbA1c (%)

Fasting glucose (mg/dL)

LDL level (%)

0.80

23.7

11.94

1.4

52

15

1.82

74

No effect

1.1

36.1

9.51

Cost-effectiveness of pycnogenol and Cost-effectiveness of pycnogenol and traditional treatments for type II diabetestraditional treatments for type II diabetes

Pycnogenol(125 mg/day)

Metformin(2,000 mg/day)

Glipizide(20 mg/day)

Repaglinide(2 mg/day)

Cost for each increment ofimprovement

HbA1c (cost fora reduction of 1 percentage point)

Fasting glucose (cost per mg/dL reduction)

LDL level (cost for each percent reduction)

Total yearly cost

$181

$10

$19

$226

$415

$11

$39

$582

$184

$5

N/A

$336

$844

$26

$98

$929

The total economic cost of diabetes in The total economic cost of diabetes in 2007 for the USA was 147 billion dollars, 2007 for the USA was 147 billion dollars, excluding the losses in quality of life. Per excluding the losses in quality of life. Per capita annual cost of health care for people capita annual cost of health care for people with diabetes was $11,744. Globally, with diabetes was $11,744. Globally, direct health care costs of diabetes range direct health care costs of diabetes range from 2.5% to 15% of annual health care from 2.5% to 15% of annual health care budgets. The significant costs of poorly budgets. The significant costs of poorly controlled diabetes clearly place a strain on controlled diabetes clearly place a strain on individuals and communities.individuals and communities.

Pycnogenol shows promise as a Pycnogenol shows promise as a supplement to traditional diabetes supplement to traditional diabetes treatments and is competitively treatments and is competitively cost-effective as compared to the cost-effective as compared to the pharmaceutical regimen. pharmaceutical regimen.

The cost and prevalence of diabetes continues The cost and prevalence of diabetes continues to increase, which makes a cost-effective to increase, which makes a cost-effective supplement like Pycnogenol very promising as supplement like Pycnogenol very promising as a mediator of this cost and should be a mediator of this cost and should be considered as a supplement for type II considered as a supplement for type II diabetics after considering the potential diabetics after considering the potential benefits.benefits.

Due to the relative cost-effectiveness of Due to the relative cost-effectiveness of Pycnogenol, supplementation should be Pycnogenol, supplementation should be beneficial for patients at risk for CVD who are beneficial for patients at risk for CVD who are maxed out on the traditional treatment but still maxed out on the traditional treatment but still exhibit uncontrolled risk factors.exhibit uncontrolled risk factors.

While CVD remains the leading cause of While CVD remains the leading cause of death in the USA, innovative and effective death in the USA, innovative and effective therapies are necessary, and Pycnogenol therapies are necessary, and Pycnogenol offers a potential cost-effective treatment that offers a potential cost-effective treatment that may help reduce the prevalence may help reduce the prevalence of CVD.of CVD.