wargovich03

8/10/2019 wargovich03

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Current Research Activitiesin Complementary and Alternative Medicine

Michael J. Wargovich, Ph.D.University of South Carolina

School of Medicine andSouth Carolina Cancer Center

Columbia, SC 29203


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Physician survey: classify treatments aslegitimate medical practice or alternative

Counseling/psychotherapy 97% 12%Diet and exercise 92 12Massage 57 42

Acupuncture 56 49Chiropractic 49 46

Homeopathic medicine 27 62Herbal medicine 3 68

Legitimate Alternative

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


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Reputable Sources forInformation on CAM

NCCAMwww.nccam.nih.gov

German Commission E Monographs American Botanical Society

Center for Mind Body Medicine(J. Gordon M.D., Arlington, VA)
http://www.nccam.nih.gov/http://www.nccam.nih.gov/


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Alternative Medicine Centers

U Oregon

Stanford

UC Davis

U T Health Science Center

U VA School of Nursing

U MD School of Medicin

Kessler InstituteFor Rehabilitation

Columbia

Harvard

Minneapolis MedicalResearch Center

**

*

*

** *

* *

UCLA

*

*

U Illinois

U Arizona

*Purdue

Johns Hopkins

Penn *

U Michigan

* *U Iowa


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Hierarchy of the Evidence

Large randomized clinical trials

Small randomized clinical trialsUncontrolled trials

Observational studies

Case Studies

Anecdotes

Weight ofScientificScrutiny


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Types of CAM Approaches

Alternative Medicine Systems

Mind-Body MethodsHerbal Therapy

Manipulative/Body Based Methods

Energy Therapies


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CAM: Whole System Approaches .


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Macrobiotics The Concept

Macrobiotics is the art and science of health andlongevity through the study and understanding of therelation and interactions between ourselves, the

foods we eat, the lifestyles we choose to lead, and theenvironments in which we live.

As what we choose to eat and drink and how we live

our lives are primary environmental factors thatinfluence our health and create who we are, themacrobiotic approach emphasizes the importance ofproper dietary and lifestyle habits .


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Macrobiotics and Cancer

CDC funded study of macrobiotics as it isused by cancer patients (U South Carolina)Anthropologic approach to determine dietaryand lifestyle aspects of macrobiotics as it ispracticed by cancer patients.Study individuals who believe they were

helped by macrobiotics, and their medicalrecords.Design future human and animal studies toinvestigate promising hypotheses.


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Ayurvedic Medicine

Science of Life Equal emphasis on:

BodyMindSpirit

Goal is harmony of the patient throughuse of diet, exercise, herbs, massageand breathing


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Qigong

Qi is the life force, and it is verysubjective to the Western mind, yet central

to Chinese medicineSeries of breathing and exercisemovements related to feeling the Qi

Research: may be used in combinationwith pain-relieving drugs in cancer patients


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Mind Body Intervention inFibromyalgia Patients

RCT of multiple component mind bodytherapy vs education

12 week trial110 patients (11/18 tender points, etc., i.e.,diagnosis of fibromyalgia)Endpoint: reduction in pain andimprovement in physical function

Clinical Trial!


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CAM: Herbal Therapy


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Soy Supplements and Reduced Riskfor Breast and Prostate Cancer

Soy is a source of natural estrogen-likecompounds collectively known as

phytoestrogensThe weak estrogenic effects may help toreduce the risk for breast and prostate

cancers.Populations with high soy intake have lowrates for these cancers


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Soy and Breast Cancer- The Facts

Soy isoflavones have been shown toreduce mammary cancer incidence in

animal studiesHypothesis: phytoestrogens compete withnatural estrogens at the receptor levelThe effect of soy on reduced risk forbreast cancer seems to be strong inpremenopausal women


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Soy and Breast Cancer- The Facts 2

Research is still equivocal on theprotective effects of soy on post-

menopausal womenOther benefits: hot flashes, boneloss, and risk for heart diseaseRisk? Could phytoestrogens stimulateER+ breast cancers? Compete withtamoxifen at ER receptor?


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Ginkgo biloba

Widely used in Europe cognitive functionNo side effects in >10,000patientsUseful in dementia and

Alzheimers Anti-inflammatory Anti-oxidant

Gingko biloba


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Ginkgo for Dementia

Multicenter clinical randomized, placebo-controlled clinical trial coordinated at the

University of Pittsburgh3000 patientsPrevention of cognitive decline in older

patients

Clinical Trial!


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Ginseng: New Uses for an Old Herb

Possible activity as a cancer preventiveKorean red ginseng inhibits breast cancer cell growthin cultureChemoprevention trial in Japan: hepatitis C inducedhepatocellular cancer

Estrogenic action may alleviate hot flashes

Potential use as an anti-inflammatory


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Ginseng Chemoprevention Trial(Japan, 2001-2007)

150 Hep C +

Cirrhotic Patients

Korean Red Ginseng (1g/d)

Placebo

Serum FP

HCC

5 yrs


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Hot flashes Use of herbalsfor relief

Black cohosh root

Korean red ginseng

Traditional Chinese Medicine


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Green Tea

Associated with reduced risk of cancer in Asiatic countries, especially Japan

Polyphenols are the responsible agentsReduce inflammation; antiproliferative, andantioxidant

Prevents cancers of skin, esophagus, andlung in animal model-at human intake levelsShould consume regularly


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Tea Hypotheses

Colon cancer may be preventable by compoundswith anti-inflammatory activity

Green and black extracts/polyphenolic fractionshave been shown to inhibit colon carcinogenesisbut the data is not consistent

Tea or its components, inhibits coloncarcinogenesis through modulation of COX, genetranscription, apoptosis, and proliferation


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9

OH

OH

OH

HO

OHO

O

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

(-)-Epigallocatechin (EGC)

(-)-Epicatechin-3-gallate (ECG)

(-)-Epicatechin (EC)

A C

B

N

N N

N

O

O

H 3 C

CH 3

CH 3

Caffeine

(1,3,7-trimethylxanthine

O

OH

OH

OH

5 3

3'

4'

Tea Antioxidants


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Evidence for Tea Drinking andPrevention of Colorectal Cancer

Ecological Studies

Cohort Studies

Case-Control Studies


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0.00

0.50

1.00

1.50

N o n - u

s e r

< 1 . 5 c u

p s / d a

y

> 1 . 5 c u

p s / d a

y

N o n - u

s e r

< 1 . 5 c u

p s / d a

y

> 1 . 5 c u

p s / d a

y

N o n - u

s e r

< 1 . 5 c u

p s / d a

y

> 1 . 5 c u

p s / d a

y

Tea Consumption at First Follow-up

R e

l a t i v e

R i s k

.

Tea Consumption and risk of Colon Cancer at firstfollow-up FFQ of NHEFS, 1971-1993

Male & Female Male Female

p (trend) < 0.001 p (trend) = 0.20

1.5none

cups/day1.5none

cups/day1.5none

cups/day

p (trend) < 0.01


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Conc lus io ns : Tea Dr inking and Riskfor Colon Canc er

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)


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St. Johns Wort

Hypericum perforatum

Widely used as anantidepressant in Europe

use of alcohol in alcoholdependent rats Acts like SSRI (Prozac)Side effect: coumadinmetabolismSide effect: tamoxifenmetabolism


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CAMs Will Need to Pass Scientific Rigor

A recent RCT of St. JohnsWort given over 4 weeks at1200 mg/d vs placebo was

conducted at 11 academicinstitutions

100 people per arm

Conclusions: SJW did notchange anxiety scores vsplaceboShelton et. al. JAMA 285:1978-1986.


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CAM: Body ManipulationMethods..


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Acupuncture for Back Pain

RCT of efficacy of acupuncture

Patients with persistent back pain

Acupuncture Vs Standard care

Clinical Trial!


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Acupuncture for Knee Osteoarthritis

RCT of efficacy of acupuncture, shamacupuncture, and education on pain relief

525 patients with 6 month history of OA

University of Maryland

Clinical Trial!


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HerbalNSAIDS...


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Epidemiology - NSAIDS

Only habitual use of aspirin has beenstrongly tied to reduced risk for colon

cancerOther NSAIDS, however, may also beshown to be protective: continual use isrecent

NSAIDS can be highly ulcerogenic especially piroxicam and indomethacin,sometimes even aspirin


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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 BaronCase-Control 0.4 Habitual Mettlin

Case-Control 0.4 Habitual Kune

Cohort 0.49 Non-ASANSAIDS for 4 y

Smalley


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How Do NSAIDs Work?

Aspirin transfers acetyl group to serine onthe cyclooxygenase enzyme, blocking its

affinity for arachidonic acid

All other NSAIDs are competitive inhibitors

of the COX enzymes


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Herbal NSAIDS

Overuse could potentially result in bleeding,prolonged platelet aggregation, and ulceration

Combined use might reduce the need for highstrength NSAIDs

Could help in long term chemoprevention trialsfor colon and breast cancer


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Devils Claw

Herb from the Kalahari desertIn Europe used for rheumatism

and arthritisShown to improve mobility andmotility of patients

Safe in the 1000-4500 mg/drange Anti-inflammatory

Harapagophytum procumbens


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Willow Bark

Long history of use as a painrelieverLittle actual research has beendone

A clinical trial in Germany foundthat 240 mg/d was effective inreducing lower back pain amongpatients with chronic back painPotential as anti-inflammatory

Salix alba


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Feverfew

Tanacetum parthenium

Has been used for treatment ofmigraine, arthritis, fever, stomach

and toothache Anti-inflammatoryMechanism unclear (non-COX?)

Inhibits platelet aggregation


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What about heart disease?

Can natural NSAIDs or other antioxidantsin foods or herbal supplements aid in theprevention of heart disease?


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Bioactive Compounds in Alliums


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Bioflavonoids

Naturally occurring chemicals present inmany fruits and vegetables

Major flavonoids in onion are quercetinand its glycoside, rutin

Can reach appreciable levels in onions buttea also is a major source


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Quercetin


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Quercetin in Foods

Major sources are tea and onions

100g of onions yields ~ 15mg of quercetin

Average intake in daily diet is about 1g/dtotal flavonoids


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Quercetin: Mechanisms of Action

Functions as an antioxidant

Inhibits proliferation of cells

Enhances immune function

( NK cells)

May act as an anti-oestrogen


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Bioflavonoids and Reduced Riskfor Heart Disease

Quercetin inhibits oxidation of LDL

cholesterol

Inhibits development of fatty streaks in

animals


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Flavonoid Intake and CHD Risk

0-19 mg/d 20-30 mg/d >31 mg/d

Number ofsubjects

268 268 269

Deaths 22 11 10

AdjustedRR 1.0 0.32 (0.15-0.68) 0.32 (0.15-0.71)

Flavonoid Intake in mg/d from diet

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


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Fruits and Vegetables: Sources ofCancer Prevention Agents

Food Source Agent ProtectsAgains t

C C C a a a b b b b b b a a a g g g e e e ,,, k k k a a a l l l e e e ,,, e e e t t t c c c ...

Isothiocyanates Lung cancer

G G Ga a ar r r l l l i i ic c c ,,, O O On n n i i io o o n n n Organosulfurcpds

Colon cancerEsophagealcancer

C C C i i i t t t r r r u u u s s s F F F r r r u u u i i i t t t s s s Monoterpenes Pancreascancer

T T T o o o m m m a a a t t t o o o e e e s s s Lycopene

carotenoids

Lung cancer

T T T e e e a a a Cathechins Skin cancer

T T T u u u m m m e e e r r r i i i c c c Curcumin Breast, skincancer

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