Current Research Activities

in Complementary and
Alternative Medicine
Michael J. Wargovich, Ph.D.
University of South Carolina
School of Medicine and
South Carolina Cancer Center
Columbia, SC 29203

Surveys of Herbal Use

1991-1998
40%
35%
30%
25%
20%
15%
10%
5%
0%
Eisenberg,
1991

Gallup, 1995

Prevention,
1997

Source: P. Brevoort, East Earth Herb

Harris, 1998

Physician survey: classify treatments as

legitimate medical practice or alternative
Legitimate Alternative

Counseling/psychotherapy
Diet and exercise
Massage
Acupuncture
Chiropractic
Homeopathic medicine
Herbal medicine

97%
92
57
56
49
27
3

From Berman et al, J Am Board Fam Prac 8:361, 1995.

12%
12
42
49
46
62
68

Reputable Sources for

Information on CAM

NCCAM

German Commission E Monographs

www.nccam.nih.gov

American Botanical Society

Center for Mind Body Medicine

(J. Gordon M.D., Arlington, VA)

www.nccam.nih.gov

Alternative Medicine Centers

U Oregon

Minneapolis Medical
Research Center
U Michigan

Harvard
*
* Columbia Penn
*U Illinois
**
* Kessler Institute
*
Purdue
For Rehabilitation
*
Johns Hopkins
U MD School of Medicine
*

Stanford

U Iowa *

UC Davis

U Arizona
*

UCLA

U VA School of Nursing

U T Health Science Center

Hierarchy of the Evidence

Large randomized clinical trials
Small randomized clinical trials
Weight of
Scientific
Scrutiny

Uncontrolled trials
Observational studies
Case Studies
Anecdotes

Types of CAM Approaches

Alternative Medicine Systems

Mind-Body Methods

Herbal Therapy

Manipulative/Body Based Methods

Energy Therapies

CAM: Whole System

Approaches.

Macrobiotics The Concept

Macrobiotics is the art and science of health and
longevity through the study and understanding of the
relation and interactions between ourselves, the
foods we eat, the lifestyles we choose to lead, and the
environments in which we live.
As what we choose to eat and drink and how we live
our lives are primary environmental factors that
influence our health and create who we are, the
macrobiotic approach emphasizes the importance of
proper dietary and lifestyle habits.

Macrobiotics and Cancer

CDC funded study of macrobiotics as it is

used by cancer patients (U South Carolina)
Anthropologic approach to determine dietary
and lifestyle aspects of macrobiotics as it is
practiced by cancer patients.
Study individuals who believe they were
helped by macrobiotics, and their medical
records.
Design future human and animal studies to
investigate promising hypotheses.

Ayurvedic Medicine

Science of Life

Equal emphasis on:

Body
Mind
Spirit

Goal is harmony of the patient through

use of diet, exercise, herbs, massage
and breathing

Herbal Antioxidants on CVD in Older

African Americans

RCT to test whether Ayurvedic herbal

preparation or antioxidant vitamins vs
placebo reduces risk of CVD
138 Older African Americans >60 y
Treatment is 12 months
Maharishi University, Iowa

Clinical Trial!

CAM: Mind Body

Approaches

Qigong

Qi is the life force, and it is very

subjective to the Western mind, yet central
to Chinese medicine
Series of breathing and exercise
movements related to feeling the Qi
Research: may be used in combination
with pain-relieving drugs in cancer patients

Mind Body Intervention in

Fibromyalgia Patients

RCT of multiple component mind body

therapy vs education
12 week trial
110 patients (11/18 tender points, etc., i.e.,
diagnosis of fibromyalgia)
Endpoint: reduction in pain and
improvement in physical function
Clinical Trial!

CAM: Herbal Therapy

Soy Supplements and Reduced Risk

for Breast and Prostate Cancer

Soy is a source of natural estrogen-like

compounds collectively known as
phytoestrogens
The weak estrogenic effects may help to
reduce the risk for breast and prostate
cancers.
Populations with high soy intake have low
rates for these cancers

Soy and Breast Cancer- The Facts

Soy isoflavones have been shown to

reduce mammary cancer incidence in
animal studies
Hypothesis: phytoestrogens compete with
natural estrogens at the receptor level
The effect of soy on reduced risk for
breast cancer seems to be strong in
premenopausal women

Soy and Breast Cancer- The Facts 2

Research is still equivocal on the

protective effects of soy on postmenopausal women
Other benefits: hot flashes, bone
loss, and risk for heart disease
Risk? Could phytoestrogens stimulate
ER+ breast cancers? Compete with
tamoxifen at ER receptor?

Ginkgo biloba

Widely used in Europe

cognitive function
No side effects in >10,000
patients
Useful in dementia and
Alzheimers
Anti-inflammatory
Anti-oxidant

Gingko biloba

Ginkgo for Dementia

Multicenter clinical randomized, placebocontrolled clinical trial coordinated at the

University of Pittsburgh
3000 patients
Prevention of cognitive decline in older
patients

Clinical Trial!

Ginseng: Ancient remedy, modern

medicine?

Ginseng: New Uses for an Old Herb

Possible activity as a cancer preventive

Korean red ginseng inhibits breast cancer cell growth

in culture
Chemoprevention trial in Japan: hepatitis C induced
hepatocellular cancer

Estrogenic action may alleviate hot flashes

Potential use as an anti-inflammatory

Ginseng Chemoprevention Trial

(Japan, 2001-2007)

Korean Red Ginseng (1g/d)

Serum FP

150 Hep C+
Cirrhotic Patients

5 yrs
Placebo

HCC

Hot flashes Use of herbals

for relief

Black cohosh root

Korean red ginseng

Traditional Chinese Medicine

Green Tea

Associated with reduced risk of cancer in

Asiatic countries, especially Japan
Polyphenols are the responsible agents
Reduce inflammation; antiproliferative, and
antioxidant
Prevents cancers of skin, esophagus, and
lung in animal model-at human intake levels
Should consume regularly

Tea Hypotheses

Colon cancer may be preventable by compounds

with anti-inflammatory activity

Green and black extracts/polyphenolic fractions

have been shown to inhibit colon carcinogenesis
but the data is not consistent

Tea or its components, inhibits colon

carcinogenesis through modulation of COX, gene
transcription, apoptosis, and proliferation

Tea Antioxidants
OH
3'

HO

O
A
OH

4'

OH OH

C
5

OH

H3C
OH

O
OH

(-)-Epigallocate chin-3-galla te (EGCG)

(-)-Epigallocate chin (EGC)
(-)-Epicate chin-3-gallate (ECG)
(-)-Epicate chin (EC)

CH3
N

N
N
CH3

Caffe ine
(1 ,3,7-trime thylxanthine )

Evidence for Tea Drinking and

Prevention of Colorectal Cancer

Ecological Studies

Cohort Studies

Case-Control Studies

Tea Consumption and risk of Colon Cancer at first

follow-up FFQ of NHEFS, 1971-1993
Male & Female

Male

Female

p (trend) < 0.01

p (trend) < 0.001

p (trend) = 0.20

1.00

0.50

0.00

cups/day

none

<1.5

>1.5

cups/day

none

<1.5

>1.5

No
nus
<
1.
er
5
cu
ps
/d
>
ay
1.
5
cu
ps
/d
ay

>1.5

No
nus
<
1.
er
5
cu
ps
>
/d
1.
ay
5
cu
ps
/d
ay

none <1.5

No
nus
<
1.
er
5
cu
ps
/d
>
ay
1.
5
cu
ps
/d
ay

Relative Risk .

1.50

Tea Consumption at First Follow-up

cups/day

Conclusions: Tea Drinking and Risk

for Colon Cancer

Tea consumption is significantly associated with reduced

colon cancer risk after adjusting for confounders

Association seen was stronger in males, but not as

significant in females

Habitual tea consumption (FFQ) is more significantly

associated with colon cancer risk than infrequent intakes
(24-hr recall)

St. Johns Wort

Widely used as an
antidepressant in Europe
use of alcohol in alcohol
dependent rats
Acts like SSRI (Prozac)
Side effect: coumadin
metabolism
Side effect: tamoxifen
metabolism

Hypericum perforatum

CAMs Will Need to Pass Scientific Rigor

A recent RCT of St. Johns

Wort given over 4 weeks at
1200 mg/d vs placebo was
conducted at 11 academic
institutions

100 people per arm

Conclusions: SJW did not

change anxiety scores vs
placebo

Shelton et. al. JAMA 285:1978-1986.

CAM: Body Manipulation

Methods..

Clinical Trial!

Acupuncture for Back Pain

RCT of efficacy of acupuncture

Patients with persistent back pain

Acupuncture Vs Standard care

Clinical Trial!

Acupuncture for Knee Osteoarthritis

RCT of efficacy of acupuncture, sham

acupuncture, and education on pain relief

525 patients with 6 month history of OA

University of Maryland

Herbal
NSAIDS...

Epidemiology - NSAIDS

Only habitual use of aspirin has been

strongly tied to reduced risk for colon
cancer
Other NSAIDS, however, may also be
shown to be protective: continual use is
recent
NSAIDS can be highly ulcerogenic
especially piroxicam and indomethacin,
sometimes even aspirin

NSAID Use and Risk for Colon Cancer

Type of study

RR

ASA Use

Author

Cohort

0.5

15x/mo

Thun

Case-Control

0.5

Continual

Baron

Case-Control

0.4

Habitual

Mettlin

Case-Control

0.4

Habitual

Kune

Cohort

0.49

Non-ASA
Smalley
NSAIDS for 4 y

How Do NSAIDs Work?

Aspirin transfers acetyl group to serine on

the cyclooxygenase enzyme, blocking its
affinity for arachidonic acid

All other NSAIDs are competitive inhibitors

of the COX enzymes

Herbal NSAIDS

Overuse could potentially result in bleeding,

prolonged platelet aggregation, and ulceration

Combined use might reduce the need for high

strength NSAIDs

Could help in long term chemoprevention trials

for colon and breast cancer

Devils Claw

Herb from the Kalahari desert

In Europe used for rheumatism
and arthritis
Shown to improve mobility and
motility of patients
Safe in the 1000-4500 mg/d
range
Anti-inflammatory

Harapagophytum
procumbens

Willow Bark

Long history of use as a pain

reliever
Little actual research has been
done
A clinical trial in Germany found
that 240 mg/d was effective in
reducing lower back pain among
patients with chronic back pain
Potential as anti-inflammatory

Salix alba

Feverfew

Has been used for treatment of

migraine, arthritis, fever, stomach
and toothache
Anti-inflammatory
Mechanism unclear (non-COX?)
Inhibits platelet aggregation

Tanacetum parthenium

What about heart disease?

Can natural NSAIDs or other antioxidants

in foods or herbal supplements aid in the
prevention of heart disease?

Bioactive Compounds in Alliums

Bioflavonoids

Naturally occurring chemicals present in

many fruits and vegetables

Major flavonoids in onion are quercetin

and its glycoside, rutin

Can reach appreciable levels in onions but

tea also is a major source

Quercetin

Quercetin in Foods

Major sources are tea and onions

100g of onions yields ~ 15mg of quercetin

Average intake in daily diet is about 1g/d

total flavonoids

Quercetin: Mechanisms of Action

Functions as an antioxidant

Inhibits proliferation of cells

Enhances immune function

( NK cells)

May act as an anti-oestrogen

Bioflavonoids and Reduced Risk

for Heart Disease

Quercetin inhibits oxidation of LDL

cholesterol

Inhibits development of fatty streaks in

animals

Bioflavonoids and Heart Disease

Prevention
Native LDL

Endothelial Cells

OXIDATION

Oxidized LDL

Flavonoid Intake and CHD Risk

Flavonoid Intake in mg/d from diet
0-19 mg/d

20-30 mg/d

>31 mg/d

Number of
subjects

268

268

269

Deaths

22

11

10

Adjusted
RR

1.0

0.32 (0.15-0.68)

0.32 (0.15-0.71)

Hertog et al. Lancet 342:1007-1011, 1993

Fruits and Vegetables: Sources of

Cancer Prevention Agents
Food Source

Agent

Cabbage, kale,
etc.
Garlic, Onion

Isothiocyanates

Citrus Fruits

Monoterpenes

Tomatoes
Tea

Lycopene
carotenoids
Cathechins

Tumeric

Curcumin

Organosulfur
cpds

Protects
Against
Lung cancer
Colon cancer
Esophageal
cancer
Pancreas
cancer
Lung cancer
Skin cancer
Breast, skin
cancer