Global Market for Oil

Palm Phenolics in
Healthcare
Dr. Robert P. Weinberg, D.O., J.D.
Research Scientist
Biomaterials Science and Engineering Lab
M.I.T.
Herbal Medicine
7000 plants have medicinal applications
25% of “modern” prescription drugs have
botanical origins
Drug = drogge = to dry
Botanical supplement sales= US$20+
billion/yr
Western Herbalists use “simples”=1 herb
Chinese and ayurvedic use many blended
together
What is a Dietary
Supplement?
Definition: (Sec 3.)
A product (other than tobacco) intended
to supplement the diet that bears or
contains one or more of the following
dietary ingredients
 Vitamins
 Minerals
 Herbs or other botanicals
 Amino acids
 Concentrate, metabolite, constituent,
extract or combination of above listed
ingredients

3
Dietary
Supplements
Traditionally defined as products made of
one or more essential nutrients such as
vitamins, minerals, and proteins, but…
DSHEA broadened definition to include
almost any product intended for
ingestion as a supplement to the diet
Must be identified on label as a D/S

4
Dietary
Supplements
Distinguished from Drugs:
Drug = article intended to diagnose,
cure, mitigate, treat, or prevent
disease
Both intended to affect structure and
function of body
Drug must undergo FDA approval after
clinical studies to determine effectiveness
and safety
D/S = no pre-market testing

5
Dietary
Supplements
Distinguished from Foods:
Foods not intended to affect structure
and function
D/S intended only to supplement diet
Not represented for use as
conventional food
Not intended as sole item of a
meal or the diet”

6
 H e rb a lPre p a ra tio n s
Te a s, in fu sio n s, d e co ctio n s – m a d e b y
ste e p in g a n d so a kin g h e rb in w a te r fo r a
fe w m in u te s
Tin ctu re s – h e rb is so a ke d in a lco h o l,
g lyce rin o r a n a lco h o l- w a te r
co m b in a tio n
E xtra ct – a filte re d o r d istille d tin ctu re
Ta b le ts a n d ca p su le s – d ryin g th e h e rb ,
p o w d e rin g it sh a p in g it in to p ills
To p ica ls – h e rb a d d e d to e m o llie n t
In je ctio n s – ve ry ra re , u su a lly o f a
 St. John’s Wort
(Hypericum)
Uses: Depression, Anxiety, Antiviral Agent
#1 Anti-depressant in Germany
Major action is the inhibition of seratonin,
norepinephrine and dopamine uptake and
down-regulation of receptors, standardized on
hypericin content
Likely safe in usual doses, in high
doses can cause severe photogenic
skin reactions
St. John’s Wort
Dosage: Daily dose of 900 mg of SJW extract
(standardized to 0.3% hypericin) found to be
equivalent to 20 mg fluoxetine
Doses up to 1800 mg tolerated in severe
depression
Likely effective in mild to moderate depression
Possibly ineffective as antiretroviral agent (and
may decrease effectiveness of HIV agents)



 Saint John’s Wort
Contraindications: Severe depression with
akinetic mutism, suicidal tendencies, severe
agitation, hypersensitivity and pregnancy
(estrogen effects)
Precautions: photosensitivity
Interactions: May precipitate hypertensive crisis
with MAO inhibitors (Mueller & Shaefer,1996)
May induce “serotonin syndrome” with SSRI’s a
with Triptans
Interferes with cyclosporine, may cause transpla
rejection
May cause hypertension with tyramine containin
foods
Safe with benzodiazapines

Ginkgo biloba
Uses: Dilates arteries, capillaries and veins
Used to increase peripheral blood flow and
improve intermittent claudication Used to
treat varicosoities, cerebral vascular
insufficiency, dementia, vertigo, and SSRI-
induced sexual dysfunction
$1 billion in US sales annually
Most frequently prescribed herb in Germany
Ginkgo biloba
Likely safe when used in appropriate doses
for up to a year, unsafe intravenously
Possibly effective in dementias (equivalent
to a six month delay in disease
progression), in improving cognitive
function in normal adults and in improving
pain free walking distances
Ineffective for memory enhancement,
ADHD, depression


Ginkgo biloba
 Precautions and interactions: Ginkolideis a selective
antagonist of platelet aggregation. Case reports of
subdural hematoma and spontaneous bleeding with
ASA use. Reports of GI disturbances and CNS symptom


 Ginkgo and caffeine may increase risk of subdural

hematomas


 Ginkgo helped SSRI induced sexual dysfunction 91% in

women, 76% in men (Cohen and Bartlik 1998)


 Use with extreme caution with stimulants

Top 10 best-selling Herbal
products
Herbal Medicinal Conditions Treated Revenue US$
Product
Glucosamine / arthritis (millions)
chondroitin
Fish oils / animal oils atherosclerosis
Coenzyme Q 10
Plant oils
Mangosteen Juice
Goji Juice
Green Tea
Echinacea
Saw Palmetto
Melat
Current Global Sales
Volume
Product 1998 2000 2005 2007 2008 2009
 What is an Herb?

Any part of
a plant
used for its
medicinal ,
flavoring , or
fragrant
property
Why People Use Them?
Consumer Lab Survey (54% had multiple
reasons)
General Health – 67%
Colds – 53%
Osteoarthritis – 39%
Energy Enhancement – 37%
Cholesterol Lowering – 29%
Cancer Prevention – 28%
Allergies – 27%
Weight Management – 25%
Herbal medicines are rapidly
increasing in
economic importance
US$ 60 000 million world
market sales for herbal
Other medicines
Countries
(including raw materials )

China

Japan
Western
Europe Canada
USA

Source: Secretariats of the Convention on Biological Diversity (CBD) 2000

 Populations Using TM/CAM Worldwide
Ethiopia 90%

Populations using Mali 75%

traditional Myanmar
70%
medicine for 70%
primary care Rwanda 60%
Tanzania 60%
Uganda
Populations in Germany 80%
developed 70%
countries who have Canada
used complementary France
49%
and alternative 48%
medicine at least Australia
once 42%
USA

Sources: Eisenberg DM et al. 1998; Health Canada, 2001;Myanmar and Mali government in 2008,
BMJ in 2003.
10/13/10
 China + India = >25% Total World Exports Value

2 0 0 6 T o ta l
S e le c te d H
Summary of South American Botanical Exports
2008 Volume (kg) and Value (USD)

S o u th A m e ri
B R A Z IL
A R G E N T IN A
 Evaluation of efficacy of herbal
medicines

T h e co m b in a tio n R e m o vin g a n y o n e
o f 4 p la n ts o f th e 4 p la n ts
cre a te s a w e a ke n s th e
p o w e rfu l e ffe ctive n e ss o f
syn e rg y fo r th e fo rm u la
m a xim u m
a n ti-tu m o u r
e ffe ct

Reported by Prof. Yeeng -chi



Cheng, Yale Medical School

2001


 Worldwide Sales of Leading Therapeutic Classes
(in BILLIONS of $USD) and Percent Growth (in local currency)

Class Therapeutic Sales Percent Sales Percent

Rank Class 1999-2000 Growth 2000-2001 Growth
1 Anti-Ulcers 15.8 12 17.4 13
2 Cholesterol & Triglycerol Reducers 13.4 21 15.9 21
3 Antidepressants 11.7 17 13.4 18
4 Calcium Antagonists (plain) 9.9 4 9.8 2
5 NSAIDS 7.7 23 9.5 26
6 ACE-Inhibitors (plain) 7.4 5 7.3 3
7 Cephalosporins & Combinations 7.3 4 6.9 -5
8 Non-narcotic Analgesics 6.2 1 6 3
9 Antipsychotics 5.1 26 6 22
10 Oral Antidiabetics 4.8 13 5.9 26

29
 European Herbals Market
Total Sale of Herbal Medicines , 2003 = € 3 . 7
billion

2% 11%
GERMANY
2% FRANCE
2%
ITALY
39%
4% POLAND
UK
5%
SPAIN
6% SWITZERLAND
BELGIUM
8% 21% NETHERLANDS
OTHERS

Source: IMS 2005

Publications on
Antioxidants
 Increase in Market Sales of
Herbal Medicines
Annual Market Sales of Herbal Medicines
$US Millions for Eight Member States

660
640 649
637
620
600
580
571
560
540
520
1999 2000 2001
The 8 member states are : the Kingdom of Bhutan, Canada, the


Czech Republic, the Islamic Republic of Iran, the Republic of

Madagascar, the Islamic Republic of Pakistan, the Republic of
Sudan, the Kingdom of Sweden

33
 G lo b a lM a rke t o f S u p p le m e n ts in

Source: PhytoPharm Consulting, NBJ, EuroConsult, WBP

2003
( Market Volume : US$ 51 Billion)
VMS Herbs Sports / Total
Specialty
North 7.9 3.9 4.5 16.3
America
Europe 5.6 6.9 2.5 15.0
Asia 1.6 5.1 1.1 7.8
Japan 3.5 2.3 1.4 7.2
South 0.8 0.6 0.3 1.7
America
Rest of the 1.2 0.8 0.6 2.6
World
Total 20.6 19.6 in retail
10.4 50.6
prices 34
Asian and Latin American Herbs Market

In 2005 (China)

§ Sales revenue from traditional Chinese medicines totalled
USD 14 billion and increased 23.81% compared to the
previous year.
§ TCM market share: 30% of total sales of medicines
In 2006 (Japan)

§ Sales revenue of Kampo medicine totalled USD 1.076 billion

§ Kampo market share: 1.67% of total medicine production
In 2007 (Brazil)

§ Sales of revenue of herbal medicines reached USD 160

millions.

Annual research report by the Chinese Traditional Medicine Industry , July 2006
Green Facts
Current Global Market: US$150 billion (As per
WHO)
Projection for 2050: US$5000 billion (As per
WHO)
Chinese Foreign Exchange: Rs 22,000 Crores
Indian Share: Rs 500 Crores
Chinese Plant Resource: 30%
Indian Plant Resource: 30%
Indian System: Time tested, trusted and well
structured
Chinese System: Not so well trusted and
structured
Some Recent Greens: Ranbaxy, HLL, Colgate
Export of Herbal
Products From
India
 Why do you use them?
1.General Health
2.Colds
3.Arthritis
4.Energy Enhancement
5.Cholesterol Lowering0% 0% 0% 0% 0% 0% 0% 0%

6.Cancer Prevention
ds

is

ies
ri t
lth

n
t
l

t
Co

en

tio

rg

en
ri n
th
ea

em

le
Ar

em
en
we
lH

Al
7.Allergies
nc

ev

ag
Lo
ra

Pr
ha

an
ne

ol
En

er

tM
Ge

er

nc
st
y

gh
rg

Ca
le

ei
e

o
En

W
Ch
8.Weight Management
 Categories of Pharmaceutical Products - 1

1) Ethical pharmaceuticals: “legend

pharmaceuticals,” patented, brand name,
prescription drugs:
Ø Lipitor, Prevacid, Risperdal, etc.
2) Generic pharmaceuticals: non-patented,
prescription drugs, with “bioequivalence” to the
legend pharmaceuticals:
Ø Atenolol, Alprazolam, Metoprolol, etc.
3) Biologics & Biological Products:
Ø Vaccines, serums, toxoids, etc.
4) Over-the-Counter Medications and
Remedies:
Ø Bayer Aspirin, Lanacaine, Zantac 75, etc.

40
 Categories of Pharmaceutical
Products - 2

5) Homeopathic Medicines (minute

quantities):
Ø Belladonna, Gelsemium, Nux Vomica, etc.
6) Vitamins & Minerals;
7) Medicinal Botanicals & Herbal Medicines:
Ø Black Cohosh, Echinacea, Ginseng, etc.
8) Botanical Extracts & Phytochemicals:
Ø p-Courmaric Acid, Chlorogenic Acid, Sulforaphane,
etc.
9) Dietary Supplements:
Ø Chondroitin Sulfate, Creatine, Shark Cartilage, etc.
10) Nutraceuticals.

41
 W hy do you use them?

0%
G eneral Health

C olds 67% 0%

Arthritis 33% 0%

0%
Energy Enhancem ent 50 %

0%
Cholesterol Lowering

0%
Cancer Prevention

Allergies0% 50 %

0%
Weight M anagem ent

0% 10% 20% 30% 40% 50% 60% 70%

Fe m ale M ale
 4 Basic Building Blocks of
Biosynthesis
1. Acetyl coenzyme A
Major role in the synthesis of phenols,
prostaglandins, macrolide antibiotics, and various
fatty acids and their derivatives.
2. Deoxyxylulose phosphate
Together with mevalonic acid is responsible for a
vast array of terpenoids and other steroids.
3. Mevalonic acid
Major precursor of cholesterol and other sterols.
4. Shikimic acid
Major precursor of phenylalanine, tyrosine, and
tryptophan and, hence, the majority of plant
alkaloids. Also involved in the biosynthesis of
lignin, flavonoids, and other aromatics.
43

 Figure 5

Funding Proposed for HHS Health

Programs in Bush Administration’s FY
2006 Budget HRSA
11 %
CDC
8%

Medicare IHS 6 %
58 % Health
Discretionary FDA 3 %
Programs NIH
9% 54 % SAMHSA
6%
Medicaid
CMS - PM
33 % 6%
SCHIP
1% OS - DM
6%
Total = $592 Total = $52 . 6
Billion Billion
Notes: Totals do not include funding for the Administration on Children and Families,
the Administration on Aging and Program Support Center. AHRQ funding is entirely
through transfers from other HHS agencies. Totals do not add to 100% due to rounding.
SOURCE: HHS, Budget in Brief FY 2006, February 2005.
 CAM use in cancer and HIV
patients
70
Massage therapy
60
50 Acupuncture
40
Chiropractic
30
20 Mind/body
therapy
10
Herbal
0
Cancer HIV patients Any CAM use
patients on HAART
N=356 N=118

Patterson (2002) J Alt and Comp Med 8(4):477-485

Risa (2002) Int J STD AIDS 13:706-713
Specific CAM therapies used in
HIV/AIDS & palliative care
Herbs & supplements
Acupuncture
Massage therapy
Naturopathic medicine
Chiropractic
Mind-Body therapy
Common uses of herbs &
supplements in HIV/AIDS care
• Omega 3 oil as an anti-inflammatory--
used to treat neuropathy
• High dose vitamin, mineral and
antioxidant therapy to build immune
system and slow disease progression
• Vitamin therapy--treats wasting, lack
of appetite, malabsorption of
nutrients
• Chinese herbs to treat diarrhea
• St. John’s Wort as antidepressant,
antiviral, anti-inflammatory agent.
 Effect of a vitamin and
mineral supplement on
infection incidence
100 n = 130 patients
90
with infection

80
70
60
50 P la c e b o
Percent

40 T re a tm e n t
30
20
10
0
N o d ia b e te s T y p e 2 d ia b e te s m e llitu s

Barringer et al (2003) Ann Int Med 138:365

Jennifer Aniston Atkins diet Madonna Yoga, herbalism

Pamela Anderson Homeopathy Sir Paul McCartney Alexander

Boris Becker Homeopathy Demi Moore Lake algae

Cherie Blair Acupuncture, Kate Moss Acupuncture

Tony Blair Homeopathy Martina Navratilova Homeopathy

Dina Carroll Reflexology Olivia Newton-John Homeopathy

Charles, Prince Magnet therapy Gwyneth Paltrow herbalism

Cher Homeopathy Brad Pitt Atkins diet

Cindy Crawford Homeopathy Sir Cliff Richard Ginseng

Sheryl Crow Eskimo diet Sarah, Duchess of York Bioenergy

Queen Elizabeth Homeopathy Arnold Schwarzenegger Breathing

Jane Fonda Homeopathy Hugo Speer Yoga

Richard Gere Breathing therapy Margaret Thatcher Ayurveda

Whoopi Goldberg Homeopathy Uma Thurman Gem therapy

Jerry Hall Homeopathy Tina Turner Homeopathy

Geri Halliwell Yoga Kate Winslet Acupuncture

Goldie Hawn Ayurveda Catherine Zeta-Jones Homeopathy

Ernst MJA 2006; 185 (11/12): 680-681

 5 Domains of CAM
Alternative Ayurveda, Chinese, Native American, Aboriginal, African,
Medical Middle Eastern, Tibetan, Central and South American cultures,
Systems Homeopathy, Naturopathy

Mind-Body cognitive-behavioral approaches, meditation, hypnosis, dance,

Interventions music, art therapy, prayer, mental healing
Biological dietary supplements, herbs, orthomolecular (varying
Based concentrations of chemicals, such as, magnesium, melatonin, and
Therapies mega-doses of vitamins), individual biological therapies (use of
Manipulative laetrile, sharkosteopathic
chiropractic, cartilage, bee pollen).
manipulation, massage
And Body-
Based Methods
Energy Therapies Qi gong, Reiki, therapeutic touch, bioelectromagnetic-based
therapies (pulsed fields, magnetic fields, or alternating current
or direct current fields)

As Defined by NCCAM
 CAM Therapies

http://nccam.nih.gov/news/camsurvey_fs1.htm#domain
CAM Therapies
Pediatric Use of CAM
Asthma 80% Reznik, 2003
(Bronx, NY)
Adolescents 54-69% Wilson, 2002 (NY)
Braun, 2005 (MN)
Special Needs 64% Sanders, 2003
(Tucson, AZ)
Rheumatology 64% Hagen, 2003
(Toronto)
ADHD 54% Chan et al, 2003
(Boston Children’s)
Emergency13-45% Losier, 2005 (Ottawa)
Lanski, 2003 (Atlanta)
Pediatric Use of CAM
Oncology 47-84% McCurdy, 2003 (WFU)
 Neuhouser, 2001 (Seattle)
 Kelly, 2000 (NYC)
Cerebral Palsy 56% Hurvitz, 2003
 Ann Arbor, MI
IBD 41% Heuschkel, 2002
 London, Boston, Detroit
Autism Spectrum 30% Levy, 2003
CHOP, PA
Preoperative 29.5% Lin, 2004
 Boston Children’s
Primary Care 12-21% Sawni, 2002 (Detroit)
Ottolini, 2001 (Wash D.C.)
Use of Herbs- Evidence?
Alternative Health supplement of the 2002
National Health Interview Survey: data on
10 common herbs
Of 30,616 adults, 19% used herbs in past
12 mo, 57% for a specific condition
Approximately 2/3 used herbs (except
Echinacea) not in accordance with
evidence based indications
 Mayo Clin Proc, May 2007;82(5): 561-566
Why Should We Care?
30,000 herbs on the market currently
Estimates of $30-40 billion dollars spent
annually Eisenberg D. et al, JAMA, Nov 11, 1998(18) 1569-
1575

Estimates of 42% of population use CAM

currently Eisenberg D. et al, JAMA, Nov 11, 1998(18) 1569-
1575

Sales of Metabolite 356 approached

$1billion in 1999 Alternative Medicine Alert, January 2000
Relacor $23 Million; 900,000 bottles by July
06

Overall Supplement Use
Why Should We Care?

600 Million Visits a Year to CAM Providers –
More Than to Primary Care Providers

Why? What is Mainstream Medicine Not
Offering to Our Patients?

E ise n b e rg D . e t a l, JA M A , N o v 1 1 , 1 9 9 8 ( 1 8 ) 1 5 6 9 -
1575
Nutritional Supplement
Recommendations
from Sloan-Kettering
 20+ billion dollars are spent each
year in the
USA on vitamins and nutritional
supplements
 Anti-oxidants are highly marketed and
are
of uncertain benefit
 Wheat Grass, Gogi, Noni, Acai,
Pomegranate,
Green Tea, Reveratrol, Vitamins A, C
and E
have not proven to be of any real
benefit
H IG H LE V E LS O F
A N T I- O X ID E N T S
PR O TEC T C A N C ER
C E LLS
A S W E LL A S
H E A LT H Y C E LLS !
Impact of CAM
CDC Report (2004)
36% of adults used some form of CAM
55% CAM + conventional treatments
26% used CAM because a medical
professional suggested it
$36-47 billion on CAM therapies in 1997
$5 billion on herbal remedies
JAMA (1998)
12.1% of population use herbal medicine
Impact of CAM
According to the National Health Statistics Report of


the CDC, in 2007:


4 out of 10 adults used a CAM therapy in the last
12 months
1 out of 9 children used CAM therapies in the last
12 months
Between 2002 and 2007 increased use was seen
among adults for acupuncture, deep breathing,
massage therapy, meditation, naturopathy, and
yoga
Diseases and Conditions
2002
1.Back pain or problem
2.Head or chest cold
3.Neck pain or problem
4.Joint pain or stiffness
5.Anxiety/depression
6.Arthritis, gout, lupus or fibromyalgia
7.Stomach or intestinal illness
8.Severe headache or migraine

*Barnes PM,et al. Complementary and alternative medicine use among adults: United States 2002; CDC
Diseases and Condition
2007
1.Back pain
2.Neck pain
3.Joint pain or stiffness
4.Arthritis
5.Other, specify
6.Anxiety
7.Cholesterol
8.Head or Chest Cold
Top 5 CAM Therapies
2002
1.Natural products, dietary supplements
2.Deep breathing exercises
3.Meditation
4.Chiropractic
5.Yoga


Top 5 CAM Therapies 2007 :

Same as 2002

*Barnes PM,et al. Complementary and alternative medicine use among adults: United States 2002; CDC
Top 10 Supplements
2002
1.Echinacea 6.St. John’s Wort
2.Ginseng 7.Peppermint
3.Ginkgo biloba 8.Fish oil/Omega 3
4.Garlic 9.Ginger
5.Glucosamine 10.Soy

Top supplement for 2007?

*Barnes PM,et al. Complementary and alternative medicine use among adults: United States 2002; CDC
Top 10 Supplements
2007
1.Fish Oil or Omega 3 or 6. Combination herb pill
DHA 7. Ginkgo biloba

2.Glucosamine 8. Chondrotin

3.Echinacea 9.Garlic Supplements

4.Flaxseed oil or pills 10.Coenzyme Q-10
5.Ginseng



 National Health
Expenditures
as a % of GDP
Oil Palm Phenolics
Dr. Robert Weinberg
Research Scientist, MIT
September 27, 2010
OPP lowers Blood
Pressure
Hypertension is a major cause of morbidity and
mortality globally, affect 250 million people
OPP significantly blocks the rise in blood
pressure in rats deficient in NO
This protection of blood pressure was dose-
dependent
Current global expenditures for anti-
hypertensive treatment are approximately
US$

Effect of OPP on Blood
Pressure
OPP reduced risk of Ventricular Fibrillation
(VF)

Ventricular Fibrillation is a leading cause of

death in individuals suffering acute
myocardial ischemia


Globally 30 million persons die annually from

Ventricular Fibrillation resulting from ischemia


OPP significantly reduces the risk of VF in rats

subjected to acute myocardial ischemia
 Effects of OPP on Cardiac
Arrhythmias
Cardioprotective Effects
of OPP
OPP results in a lower mean duration of VT
 in treated rats (control, 120.5±35.9 vs OPP
85.2±26.1 s)
OPP substantially reduces the incidence of VF
 (controls, 91% vs. OPP, 52%)
OPP shortens duration of VF (control 99.8±21.2
 vs. OPP 47.5±15.5)
OPP substantially reduces overall mortality
from myocardial ischemia (control 9/23 [40%]
vs
 OPP 5/25 [20%])
OPP protects against
Diabetes
Globally Diabetes mellitus causes substantial
morbidity and mortality affecting 180 million
persons


The Nile Grass rat is an animal model of

Diabetes mellitus and metabolic syndrome in
man


OPP prevents the development of Diabetes in

the Nile Grass rat
Anti-Diabetic effects of
OPP
OPP blocks Cancer Tumor
Growth
Globally cancer is a leading cause of death
In 2009, cancer killed over 14 million persons
In 2009, over 30 million were diagnosed with
cancer
Although the specific organ cancers vary from
country to country, it presents a substantial
annual healthcare burden costing over US$30
billion
OPP substantially reduces cancer tumor growth
in mice inoculated with myeloma tumors
Effect of OPP on growth of Myeloma
tumors
OPP blocks Atherosclerosis progression
Globally cardiovascular disease (CVD) resulting
from atherosclerosis is a major cause of
morbidity and mortality
Annually over 12 million persons die from CVD
resulting from atherosclerosis
Globally, in 2009, over 45 million persons are
impaired or disabled by CVD
In a rabbit model of CVD, OPP blocks the
progression of atherosclerosis
Effects of OPP on
Atherosclerosis