Linus Pauling Institute: CHLOROPHYLL AND CHLOROPHYLLIN

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[sSRI-Research] Linus Pauling Institute: CHLOROPHYLL AND

CHLOROPHYLLIN

 

 

 

http://lpi.oregonstate.edu/infocenter/phytochemicals/chlorophylls/index.html

 

CHLOROPHYLL AND CHLOROPHYLLIN

 

Chlorophyll is the pigment that gives plants and algae their green

color. Plants use chlorophyll to trap light needed for photosynthesis

(1). The basic structure of chlorophyll is a porphyrin ring similar to

that of heme in hemoglobin, although the central atom in chlorophyll

is magnesium instead of iron. The long hydrocarbon (phytol) tail

attached to the porphyrin ring makes chlorophyll fat-soluble and

insoluble in water. Two different types of chlorophyll (chlorophyll a

and chlorophyll b) are found in plants (structures of natural

chlorophylls). The small difference in one of the side chains allows

each type of chlorophyll to absorb light at slightly different

wavelengths. Chlorophyllin is a semi-synthetic mixture of sodium

copper salts derived from chlorophyll (2, 3). During the synthesis of

chlorophyllin, the magnesium atom at the center of the ring is

replaced with copper and the phytol tail is lost. Unlike natural

chlorophyll, chlorophyllin is water-soluble. Although the content of

different chlorophyllin mixtures may vary, two compounds commonly

found in commercial chlorophyllin mixtures are trisodium copper

chlorin e6 and disodium copper chlorin e4 (structures of two

commercial chlorophyllins).

 

Biological Activities

 

Complex Formation with Other Molecules

 

Chlorophyll and chlorophyllin are able to form tight molecular

complexes with certain chemicals known or suspected to cause cancer,

including polyaromatic hydrocarbons found in tobacco smoke (4), some

heterocyclic amines found in cooked meat (5), and aflatoxin-B1 (6).

See a computer-generated molecular model of a

chlorophyllin-aflatoxin-B1 complex. The tight binding of chlorophyll

or chlorophyllin to these potential carcinogens may interfere with

their absorption from the gastrointestinal tract and reduce the amount

that reaches susceptible tissues (7).

 

Antioxidant Effects

 

Chlorophyllin can neutralize several physically relevant oxidants in

the test tube (8, 9), and limited data from animal studies suggest

that chlorophyllin supplementation may decrease oxidative damage

induced by chemical carcinogens and radiation (10, 11).

 

Modification of the Metabolism and Detoxification of Carcinogens

 

In order to initiate the development of cancer, some chemicals

(procarcinogens) must first be metabolized to active carcinogens that

are capable of damaging DNA or other critical molecules in susceptible

tissues. Since enzymes in the cytochrome P450 family are required for

the activation of some procarcinogens, inhibition of cytochrome P450

enzymes may decrease the risk of some types of chemically-induced

cancers. Test tube studies indicate that chlorophyllin may decrease

the activity of cytochrome P450 enzymes (4, 12). Phase II

detoxification enzymes promote the elimination of potentially harmful

toxins and carcinogens from the body. Limited data from animal studies

indicate that chlorophyllin may increase the activity of the phase II

enzyme quinone reductase (13).

 

Disease Prevention

 

Aflatoxin-Associated Liver Cancer

 

Aflatoxin-B1 (AFB1) is a liver carcinogen produced by certain species

of fungus and found in moldy grains and legumes, such as corn, peanuts

and soybeans (2, 7). In hot, humid regions of Africa and Asia with

inadequate grain storage facilities, high levels of dietary AFB1 are

associated with increased risk of hepatocellular carcinoma (liver

cancer). Moreover, the combination of hepatitis B infection and high

dietary AFB1 exposure increases the risk of hepatocellular carcinoma

still further. In the liver, AFB1 is metabolized to a carcinogen

capable of binding DNA and causing mutations. In animal models of

AFB1-induced liver cancer, administration of chlorophyllin at the same

time as dietary AFB1 exposure significantly reduced AFB1-induced DNA

damage in the livers of rainbow trout and rats (14, 15), and

dose-dependently inhibited the development of liver cancer in trout (16).

 

Because of the long time period between AFB1 exposure and the

development of cancer in humans, an intervention trial might require

as long as twenty years to determine whether chlorophyllin

supplementation can reduce the incidence of hepatocellular carcinoma

in people exposed to high levels of dietary AFB1. However, a biomarker

of AFB1-induced DNA damage (AFB1-N7-guanine) can be measured in the

urine, and high urinary levels of AFB1-N7-guanine have been associated

with significantly increased risk of developing hepatocellular

carcinoma (17). In order to determine whether chlorophyllin could

decrease AFB1-induced DNA damage in humans, a randomized

placebo-controlled intervention trial was conducted in 180 adults

residing in a region China where the risk of hepatocellular carcinoma

is very high due to unavoidable dietary AFB1 exposure and a high

prevalence of chronic hepatitis B infection (18). Participants took

either 100 mg of chlorophyllin or a placebo before meals three times

daily. After 16 weeks of treatment, urinary levels of AFB1-N7-guanine

were 55% lower in those taking chlorophyllin than those taking the

placebo, suggesting that chlorophyllin supplementation before meals

can substantially decrease AFB1-induced DNA damage. Although a

reduction in hepatocellular carcinoma has not yet been demonstrated in

humans taking chlorophyllin, scientists are hopeful that chlorophyllin

supplementation will provide some protection to high-risk populations

with unavoidable dietary AFB1 exposure (7). For more information about

the Chlorophyllin Clinical Trial see Dr. George Bailey's article in

the Fall/Winter 2002 Linus Pauling Institute Newsletter.

 

It is not known whether chlorophyllin will be useful in the prevention

of cancers in people who are not exposed to significant levels of

dietary AFB1, as is the case for most people living in the U.S. Many

questions remain to be answered regarding the exact mechanisms of

cancer prevention by chlorophyllin, the implications for the

prevention of other types of cancer, and the potential for natural

chlorophylls in the diet to provide cancer protection. Scientists from

the Linus Pauling Institute's Cancer Chemoprotection Program have been

awarded a grant from the National Cancer Institute to study these

questions and others aimed at identifying dietary phytochemicals

effective in reducing the risk of lung, stomach, and breast cancers

induced by polyaromatic hydrocarbons, colorectal cancer induced by

heterocyclic amines, as well as liver cancer induced by AFB1. For more

information about the Linus Pauling Institute's Cancer Chemoprotection

Program see Dr. David Williams' article in the Spring/Summer 1999

Linus Pauling Institute Newsletter and recent updates by Dr. Rod

Dashwood in the Fall/Winter 2003 Linus Pauling Institute Research Report.

 

 

THERAPEUTIC USES OF CHLOROPHYLLIN

 

Internal Deodorant

 

Observations in the 1940s and 1950s that topical chlorophyllin had

deodorizing effects on foul-smelling wounds led clinicians to

administer chlorophyllin orally to patients with colostomies and

ileostomies in order to control fecal odor (19). While early case

reports indicated that chlorophyllin doses of 100-200 mg/day were

effective in reducing fecal odor in ostomy patients (20, 21), at least

one placebo-controlled trial found that oral chlorophyllin (75 mg

three times daily) was no more effective than placebo in decreasing

fecal odor assessed by colostomy patients. Several case reports have

been published indicating that oral chlorophyllin (100-300 mg/day)

decreased subjective assessments of urinary and fecal odor in

incontinent patients (19, 22). Trimethylaminuria is a hereditary

disorder characterized by the excretion of trimethylamine, a compound

with a " fishy " or foul odor. A recent study in seven Japanese patients

with trimethylaminuria found that three weeks of oral chlorophyllin

therapy (60 mg three times daily) significantly decreased urinary

trimethylamine levels (23).

 

Wound Healing

 

Research in the 1940s indicating that chlorophyllin solutions slowed

the growth of certain anaerobic bacteria in the test tube and

accelerated the healing of experimental wounds in animals led to the

use of topical chlorophyllin solutions and ointments in the treatment

of persistent open wounds in humans (24). During the late 1940s and

1950s, a series of largely uncontrolled studies in patients with

slow-healing wounds, such as vascular ulcers and pressure (decubitus)

ulcers, reported that the application of topical chlorophyllin

promoted healing more effectively than other commonly used treatments

(25, 26). In the late 1950s, chlorophyllin was added to papain and

urea-containing ointments used for the chemical debridement of wounds

in order to reduce local inflammation, promote healing and control

odor (19). Chloriphyllin-containing papain/urea ointments are still

available in the U.S. by prescription (27).

 

Sources

 

Chlorophylls

 

Chlorophylls are the most abundant pigments in plants. Dark green

leafy vegetables like spinach are rich sources of natural

chlorophylls. Green algae like chlorella are often marketed as

supplemental sources of chlorophyll. Because natural chlorophyll is

not as stable as chlorophyllin and is much more expensive, most

over-the-counter chlorophyll supplements actually contain chlorophyllin.

 

Chlorophyllin

 

Oral preparations of sodium copper chlorophyllin (also called

chlorophyllin copper complex) are available in supplements and as an

over-the-counter drug (Derifil) used to reduce odor from colostomies

or ileostomies or to reduce fecal odor due to incontinence (28).

Sodium copper chlorophyllin may also be used as a color additive in

foods, drugs, and cosmetics (29).

 

Safety

 

Natural chlorophylls are not known to be toxic, and no toxic effects

have been attributed to chlorophyllin despite more than 50 years of

clinical use in humans (7, 19, 24). When taken orally, chlorophyllin

may cause green discoloration of urine or feces or yellow or black

discoloration of the tongue (30). There have also been occasional

reports of diarrhea related to oral chlorophyllin use. When applied

topically to wounds, chlorophyllin has been reported to cause mild

burning or itching in some cases (31). Oral chlorophyllin may result

in false positive results on guaiac card tests for occult blood (32).

Since the safety of chlorophyll or chlorophyllin supplements has not

been tested in pregnant or lactating women, they should be avoided by

pregnant or breastfeeding women.

 

Summary

 

.. Chlorophyll a and chlorophyll b are natural, fat-soluble

chlorophylls found in plants. (More Information)

 

.. Chlorophyllin is a semi-synthetic mixture of water-soluble sodium

copper salts derived from chlorophyll. (More Information)

 

.. Chlorophyllin has been used orally as an internal deodorant and

topically in the treatment of slow-healing wounds for more than 50

years without any serious side effects. (More Information)

 

.. Chlorophylls and chlorophyllin form tight molecular complexes with

some chemicals known or suspected to cause cancer, and in doing so,

may block their carcinogenic effects. No carefully controlled studies

have been undertaken to determine whether a similar mechanism might

limit uptake of required nutrients or minerals. (More Information)

 

.. Supplementation with chlorophyllin before meals substantially

decreased a urinary biomarker of aflatoxin-induced DNA damage in a

Chinese population at high risk of liver cancer due to unavoidable

dietary aflatoxin exposure. (More Information)

 

.. Scientists are hopeful that chlorophyllin supplementation will be

helpful in decreasing the risk of liver cancer in high-risk

populations with unavoidable dietary aflatoxin exposure. However, it

is not yet known whether chlorophyllin or natural chlorophylls will be

useful in the prevention of cancers in people who are not exposed to

significant levels of dietary aflatoxin. (More Information)

 

REFERENCES

 

 

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Written by:

Jane Higdon, Ph.D.

Linus Pauling Institute

Oregon State University

 

Reviewed by:

Roderick H. Dashwood, Ph.D.

Chief, Cancer Chemoprotection Program, Linus Pauling Institute

Professor of Environmental & Molecular Toxicology

Leader, Environmental Mutagenesis & Carcinogenesis Core, Environmental

Health Sciences Center

Oregon State University

 

Last updated 07/16/2004 Copyright 2004 Linus Pauling Institute

 

 

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