THE MOSS REPORTS Newsletter (10/24/04)

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THE MOSS REPORTS Newsletter (10/24/04)

 

 

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Ralph W. Moss, Ph.D. Weekly CancerDecisions.com

Newsletter #155 10/24/04

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THE MOSS REPORTS

 

 

This week I conclude a two-part discussion of the re-emergence of

chaparral, an herbal treatment for cancer which was once considered by

mainstream medicine to be nothing but a cruel and dangerous fraud. Now, a

derivative of chaparral, M4N, is being tested in clinical trials for the

treatment of head and neck cancer, a type of cancer that is notoriously

resistant to standard therapies.

 

In more than thirty years of studying and chronicling developments in

the field of cancer therapy I have seen many useful alternative

treatments at first mercilessly vilified and driven underground, only to

resurface years later when science eventually confirms that the active

principle of such a treatment really does have some recognizable,

quantifiable effect against cancer cells.

 

The fruit of my long career in this field is The Moss Reports, a

comprehensive library of guides to both the conventional and alternative

treatment of over 230 different kinds of cancer. For cancer patients

there

can be few more useful guides and decision-making tools than a Moss

Report.

 

To order a Moss Report please visit our website,

www.cancerdecisions.com, or call Diane at 1-800-980-1234 (814-238-3367

from outside the US).

 

We look forward to helping you.

 

 

 

HERB-DERIVED DRUG FIGHTS HEAD-AND-NECK CANCER, PART TWO

 

 

 

Contesting Claims

 

 

Scientific interest in chaparral surged in the late 1960s after an

85-year-old man came to the University of Utah with a proven malignant

melanoma of the right cheek. He underwent four operations for this deadly

form of skin cancer, but a tumor reappeared after each operation, and

eventually the cancer spread to his neck. By the time he saw Dr. Charles

Smart at the University of Utah, the lesion measured 3 by 4 centimeters

(nearly 2 inches across).

 

In light of the poor results from the previous operations, the patient

decided to avoid further surgery and returned home. He began taking

chaparral tea in November 1967, and by February 1968 his facial lesion

had

decreased to the size of a dime, and the neck mass had also

disappeared. In September 1968 he returned to be examined, and by that

time the

lesion had shrunk to a tiny 2-3 millimeters, and there were no masses in

his neck. He looked much better and had gained twenty-five pounds. Even

the American Cancer Society conceded that he had " marked regression of

the cancer " (ACS 1971).

 

Based on this remarkable case, Dr. Smart and colleagues then carried

out a study with fifty-nine cancer patients who took chaparral tea. Of

these, forty-five completed the study, and four showed significant tumor

regressions. Of the patients who responded with tumor regression, two

had malignant melanoma, one had choriocarcinoma that had spread to the

lungs, and one had widespread lymphoma. One of the melanoma patients

experienced a 95 percent regression, whereupon the remaining growth was

removed by surgical excision (Smart 1970).

 

Two other patients also had striking regression of their cancers, but

were not included in the final tally. However, some patients

paradoxically showed an apparent increase in tumor activity. This may

be because

at low doses chaparral or NDGA is said to stimulate tumor growth. It is

only at higher dose levels that it begins to produce tumor regression

(Pelton 1994)

 

A scientific article by Drs. Dean Burk and Mark Woods of the National

Cancer Institute called NDGA " the penicillin of quinones, " because the

compound has a wide range of anticancer properties and is relatively

nontoxic. They concluded that laboratory tests had shown that NDGA was

one

of the most potent cancer-killing anti-metabolites, in spite of what

they judged to be its relatively low toxicity (Burk 1963).

 

Chaparral tea was subsequently investigated by scientists at other

medical centers, including by the chairman of the biochemistry department

at the University of Nevada. An Arizona scientist received an $81,000

contract to investigate treatments which might be developed from desert

plants, and doctors in Reno began to use chaparral tea on their cancer

patients.

 

In 1971, while research was still underway, the ACS placed chaparral

tea on its unproven methods lists - a harsh blow at the time for any

further investigations. In their statement of the time, the ACS wrote:

 

" After careful study of the literature and other information available

to it, the American Cancer Society does not have evidence that

treatment with chaparral tea results in objective benefit in the

treatment of

cancer in human beings " (ACS 1971:55).

 

This did not stop many people from trying to use the herb for cancers

of every type. Alarmed over the growing popularity of the herb, and much

later over several reports of liver damage following its use, the Food

and Drug Administration (FDA) negotiated with food supplement

manufacturers in 1992 to persuade them to not sell the product. Rather

than face

an outright ban, most of them readily complied.

 

The FDA website currently states:

 

" Chaparral, commonly called the creosote bush, is a desert shrub with a

long history of use as a traditional medicine by Native Americans.

Chaparral is marketed as a tea, as well as in tablet, capsule, and

concentrated extract form, and has been promoted as a natural antioxidant

`blood purifier,' cancer cure, and acne treatment.

 

" At least six cases (five in the United States and one in Canada) of

acute non-viral hepatitis...have been associated with the consumption of

chaparral as a dietary supplement. Additional cases have been reported

and are under investigation. In the majority of the cases reported thus

far, the injury to the liver resolves over time, after discontinuation

of the product. In at least two patients, however, there is evidence

that chaparral consumption caused irreversible liver damage. One patient

suffered terminal liver failure requiring liver transplant.

 

" Most of these cases are associated with the consumption of single

ingredient chaparral capsules or tablets; however, a few of the more

recent

cases appear to be associated with consumption of multi-ingredient

products (capsules, tablets or teas) that contain chaparral as one

ingredient. Chemical analyses have identified no contaminants in the

products

associated with the cases of hepatitis. Products from at least four

different distributors and from at least two different sources have been

implicated thus far. "

 

The present-day ACS statement also focuses on the toxicity of the herb:

" Chaparral is considered a dangerous herb that can cause irreversible,

life-threatening liver damage. The FDA has cautioned against the

internal use of chaparral. Research has not found it to be an effective

treatment for cancer or any other disease. A study of

nordihydroguaiaretic

acid (NDGA), one of the chemicals in chaparral, concluded that it was

not useful in treating people with cancer. Researchers continue to study

NDGA in laboratory experiments. "

 

This seems to be a remarkably one-sided evaluation of the available

data on chaparral's effects on cancer. For example, no reference is given

for the " study " in question, and one wonders what research it is based

on. Most of the in vitro and in vivo studies cited in a comprehensive

2004 Institute of Medicine monograph are more positive than negative in

nature, at least in regard to potential efficacy (Committee 2004). The

only clinical trial mentioned by the IOM is the aforementioned 1970

study by Dr. Smart.

 

In addition, PubMed (the National Library of Medicine's comprehensive

database of medical and scientific literature) also does not contain any

negative clinical trials of chaparral or NDGA among its 15 million

articles. To characterize chaparral as " not useful " seems tendentious. In

fact, it is sad to see the modern-day ACS reverting to its `imaginative'

negative evaluations of the past (such as I analyzed in detail in my

book, The Cancer Industry).

 

But just how toxic is chaparral?

 

It is universally assumed that the use of chaparral constitutes a

potential threat to the liver. The first report I know of detailing liver

toxicity dates from the early 1980s. This concerned a woman who used

tablets of chaparral leaf to treat a benign breast lump. She took 15

tablets per day, beginning in April 1983. By July she experienced nausea,

loss of appetite, and gastric pain. By August she reduced the number of

tablets to one per day, which cleared up her abdominal symptoms. She then

once again increased the dosage to 7 per day, and experienced more

severe problems. At this point she checked into a hospital and was

found to

be suffering from liver damage. A biopsy showed a 60-percent loss of

essential liver cells. Fortunately, she recovered fully from the liver

damage, and was discharged.

 

There are other cases as well. A review article by FDA scientists

stated that eighteen cases of adverse events associated with the

ingestion

of chaparral had been reported to the FDA between 1992 and 1994. " There

was evidence of hepatotoxicity [liver damage, ed.] in 13 [of these,

ed.] cases....Jaundice with a marked increase in serum liver chemistry

values, occurred 3 to 52 weeks after the ingestion of chaparral, and it

resolved 1 to 17 weeks after most individuals stopped their intake of

chaparral....n 4 individuals, there was progression to cirrhosis; and

in 2 individuals, there was acute fulminant liver failure that required

liver transplants " (Sheikh 1997).

An even more alarming report came from surgeons at the Oregon Health

and Science University in Portland, OR, in 2003. They stated that ten out

of twenty of the liver transplant patients there who presented with

fulminant hepatic failure [FHF – a particularly sudden and catastrophic

form of liver failure, ed.] were recent or active users of potentially

hepatotoxic supplements, including chaparral. The surgeons strongly urged

enhanced public awareness of the danger of these supplements and an

" increased regulatory oversight of their use " (Estes 2003).

However, a small study in the Journal of Alternative and Complementary

Medicine raises some questions about the frequency of this type of

adverse reaction. Two naturopaths in Sedona, Arizona followed four

patients

who were receiving low-dose chaparral for 22 months. The patients had

complete blood counts and full blood chemistry panels both before and

after treatment. According to the authors there was no indication of

liver damage from use of Larrea [i.e., chaparral] even though one of

these

patients was already taking medications with a significant potential

for hepatotoxicity.

" No patient in the study, whether using Larrea for short term or long,

internally or externally, showed any sign of organ damage during the

period of follow-up, " the authors wrote. They concluded that " relatively

small intakes of Larrea tincture, or topical application of extracts in

Ricinus oil, are safe when prescribed by a clinically trained botanical

prescriber. "

However, they agreed that " Larrea should be used with caution in

persons with a history of previous, or current, liver disease. It may be

preferable to avoid the use of Larrea capsules because they have been

associated with potentially dangerous overdosing " (Heron 2001).

Extract Vs. Herb

The debate concerning the use of whole herbs vs. using purified

constituents is a very old one, which effectively split herbalists in

the 19th

century (see my book, Herbs Against Cancer). NDGA is only one of the

many chemicals in chaparral. According to Dr. James Duke's US Department

of Agriculture ethnobotanical database, there are at least a dozen

others, some of which have been shown to have anticancer activity (USDA

2004). A 2001 study from the University of Buenos Aires, Argentina,

showed

that a water extract of chaparral (L. divaricata) had a much greater

ability to kill lymphoma cells than did NDGA alone. The extract killed

cancer cells in at least three separate ways: by increasing cAMP levels,

by inhibiting protein kinase C (PKC) activity, and by influencing

cellular calcium influx.

By comparison, NDGA alone failed to influence two out of three of those

mechanisms. NDGA could only work, the researchers surmised, by

inhibiting PKC. In addition, the amount of NDGA detected in the water

extract

was insufficient to account for the plant extract's anticancer activity.

Although it is possible that NDGA " could have an additive effect on the

activity of other compounds " (Anesini 2001), using NDGA as a stand-in

for chaparral (and then declaring the herb itself ineffective) is a

sleight-of-hand that most people can quickly see through.

This PubMed listed reference also challenges the idea that chaparral's

anticancer activity is solely due to its best known component, NDGA. It

does not take a conspiracy theorist to see that an unpatentable herb

that sells for under $10 per pound does not have the same economic

attractiveness as a purified, modified, synthesized drug that could

eventually earn investors billions of dollars in returns.

Recommendations

I am excited by the revival of chaparral, in any form, as a cancer

treatment. It is a bittersweet development, however, since the herb

and its

derivatives should have been more carefully tested back in the 1960s

and 1970s, the way that NCI biochemist, Dean Burk, PhD, then urged. But

does this mean that readers should rush out to take this herb?

Some readers, impatient with the slow pace of medical research and

eager to find a cure for medical conditions for which no conventional

treatment has proven effective, might be tempted to self-medicate with

chaparral. Let me therefore make my position clear:

I STRONGLY DISCOURAGE ANYONE FROM USING CHAPARRAL AS A SELF-HELP

TREATMENT AT THE PRESENT TIME.

That is because, despite the herb's great promise, the possibility of

liver damage or other serious toxicity is simply too great to be

ignored. In fact, I would go further. While I generally respect the

judgment

of most qualified herbalists, I would not take this herb even if it were

recommended by an herbal practitioner. Its toxicity profile is just too

uncertain to run the risk of serious harm to the liver.

On the other hand, I strongly urge further research not only on NDGA

and M4N, but also on extracts of the whole chaparral plant. A concerted

effort to explore the effects of the whole herb and its extracts, with

informed consent and proper institutional review board approval and

oversight, should be strongly supported and encouraged.

I will admit to mixed feelings about M4N. Of course, I certainly

welcome any new anticancer drug and am excited by the two Phase I

clinical

studies that have been reported in 2004. But I would also like to see the

whole chaparral plant investigated as a cancer treatment, picking up

where Drs. Charles Smart, Dean Burk and others left off over three

decades ago. Such a study could be very illuminating. However, any

clinical

study of the herb would of course have to include meticulous liver

function monitoring to make sure that no hepatic damage is taking place.

But even these preliminary results with M4N go a long way towards

vindicating the use of one of Native America's oldest alternative cancer

treatments. Once again, the wisdom of folk medicine shines through.

--Ralph W. Moss, PhD

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References:

Anyone seriously interested in pursuing research into chaparral should

consult the excellent 78-page booklet on the topic from the Institute

of Medicine:

Committee on the Framework for Evaluating the Safety of Dietary

Supplements. Food and Nutrition Board, Board on Life Sciences, US

Institute of

Medicine, Prototype Monograph on Chaparral (2004). Retrieved August 19,

2004 from:

http://www.iom.edu/includes/DBFile.asp?id=19556

ACS (American Cancer Society). Unproven methods of cancer treatment:

chaparral tea. New York, NY: American Cancer Society, 1970.

Anesini C, Genaro A, Cremaschi G, et al. " In vivo " and " in vitro "

antitumoral action of Larrea divaricata. Physiol Pharmacol Ther Latinoam

1996;46:33-40.

Anesini C, Genaro A, Cremaschi G, Sterin Borda L, Borda E.

Antimitogenic effect of Larrea divaricata Cav.: participation in

arachidonate

metabolism. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol

1999;46:245-52.

Anesini C, Turner S, Borda E, Ferraro G, Coussio J. Effect of Larrea

divaricata Cav. extract and nordihydroguaiaretic acid upon peroxidase

secretion in rat submandibular glands. Pharmacol Res 2004;49:441-448.

Burk D, Woods M. Hydrogen peroxide, catalase, glutathione peroxidase,

quinones, NDGA, and phosphopyridine nucleotides in relation to X-ray

action on cancer cells. Rad Res Suppl 1963;3:212–246.

Chen H, Teng L, Li J-H, Tseng WN, Mold DE, Huang RC. Antiviral

activities of methylated nordihydroguaiaretic acids (II) Targeting herpes

simplex virus replication by mutation insensitive transcription inhibitor

tetra-O-methyl NDGA. J. Medicinal Chem 1998;41:3001-3007.

Craigo J, Callahan M, Huang RC, Delucia AL. Inhibition of human

papilloma virus type 16 gene expression by nordihydroguaiaretic acid

plant

lignan derivatives. Antiviral Res 2000;47:19-28.

Dunphy FR, Dukelow KK, Provenzal J, Crawford J.Phase I clinical results

of intralesional injection of tetra-o-methy nordihydroguaiaretic acid

(M4N) in refractory head and neck cancer. ASCO Annual Meeting. Abstract

No: 5614. Retrieved on August 20, 2004 from:

http://asco.org/ac/1,1003,_12-002644,00.asp

Estes JD, Stolpman D, Olyaei A, et al. High prevalence of potentially

hepatotoxic herbal supplement use in patients with fulminant hepatic

failure. Arch Surg 2003;138:852-858.

Gisvold et al., Lignans from Larrea divaricata. J Pharmaceut Sci

1974;63:1905-1907.

Gnabre JN, Huang RC, Burns JJ, et al., Characterization of anti-HIV

lignans from Larrea tridentata. Tetrahedron 1995:51:12203-12210.

Gnabre JN, Bates RB, Caldera S, Huang RC. Chemical structure of

HIV-inhibitory lignans from Larrea tridentata. Tetrahedron

1995;51:12203-12210.

Gnabre JN, Brady J, Clanton D, et al. Inhibition of human

immunodeficiency virus type 1 transcription and replication by DNA

sequence-selective plant lignans. Proc Natl Acad Sci USA

1995;92:11239-11243.

Gnabre JN, Ito Y, Ma Y, Huang RC. Isolation of anti-HIV-1 lignans from

Larrea tridentata counter-current Chromatography, Journal of

Chromatography A 1996;719:353-364.

Heller JD, Kuo J, Wu TC, Kast WM, Huang RCC. Tetra-O-methyl

nordihydroguaiaretic acid induces G2 arrest in mammalian cells.

Cancer Res

2001;61;5499-5504.

Heron S, Yarnell E. The safety of low-dose Larrea tridentata (DC)

Coville (creosote bush or chaparral): a retrospective clinical study. J

Altern Complement Med 2001;7:175-85.

Huang RCC, Li Y, Giza PE, et al. Novel antiviral agent tetraglycylated

nordihydroguaiaretic acid hydrochloride as a host-dependent viral

inhibitor. Antiviral Res. 2003;58:57-64.

Hwu JR, Tseng WN, Gnabre J, Giza P, Huang RC. Antiviral activities of

methylated nordihydroguaiaretic acids. 1. Synthesis, structure

identification, and inhibition of tat-regulated HIV transactivation. J

Med Chem

1998;41:2994-3000.

Newall, C; Anderson, L; Phillipson, J. Herbal Medicines: A Guide for

Healthcare Professionals. London: Pharmaceutical Press, 1996.

Park R, Giza PE, Mold DE, Huang RCC. Inhibition of HSV-1 replication

and reactivation by the mutation-insensitive transcription inhibitor

tetra-O-glycyl-nordihydroguaiaretic acid. Antiviral Res 2003;58, 35-45.

Pelton, Ross and Overholser, Lee. Alternatives in Cancer Therapy. New

York: Fireside, 1994.

Perry CW, Kalniss, MV, Deitcher, KH. Synthesis of Lignans. I.

Nordihydroguaiaretic Acid. Suppl.1. J Org Chem 1972;37:4371-4376.

Reuters News Service. Desert Shrub May Help Some Cancer Patients -

Study, August 10, 2004. Retrieved August 19, 2004 from:

http://www.reuters.co.uk/newsArticle.jhtml?type=healthNews & storyID=5928053§ion=n\

ews

Sheikh NM, Philen RM, Love LA. Chaparral-associated hepatotoxicity.

Arch Intern Med 1997;157:913-919.

Smart CR, Hogle HH, Vogel H, Broom AD, Bartholomew D. Clinical

experience with nordihydroguaiaretic acid-- " Chaparrel tea " in the

treatment of

cancer. Rocky Mt Med J 1970;67:39–43.

United States Department of Agriculture (USDA). Dr. Duke's

Phytochemical and Ethnobotanical Databases. Retrieved August 20, 2004

from:

http://www.ars-grin.gov/duke/

Zamora JM. Cytotoxic, Antimicrobial and Phytochemical Properties of

Larrea Tridentata Cav. Auburn, AL: Auburn University. Dissertation, 1984.

Resources:

BioCure Medical LLC

940 Main Campus Dr., Suite 170

Raleigh, NC 27606

Phone: (919) 821-5204

Fax: (919) 821-5309

http://www.erimos.com/

James Oliver, PharmD (919-833-7196)

joliver

Clinical Trial:

Medical University of South Carolina (MUSC)

Charleston, SC 29475

Terry Day, MD, Principal Investigator

Betsy Sass, RN: 843-792-6325

sasse

Terry A. Day, MD

Head and Neck Surgery (ENT)

MUSC Medical Center

135 Rutledge Ave., Suite 1130

PO Box 250550

Charleston, SC 29425

1-800-424-MUSC (843-792-1414 in the Charleston area)

Email Address: dayt

Miscellaneous links:

Johns Hopkins' statement on Indian clinical trial:

http://www.jhu.edu/news_info/news/home01/jul01/india.html

Huge demonstrations in India:

http://www.flonnet.com/fl1817/18170110.htm

BioCure Medical study of M4N:

http://www.clinicaltrials.gov/ct/show/NCT00057512?order=1

Author of the ASCO paper:

Frank Dunphy, MD

DUMC 3685

Durham, NC 27710

Phone: (919) 684-5621

Fax: (919) 681-5864

Ru Chih Huang, PhD

Department of Biology

Johns Hopkins University

Phone: (410) 516-5181

Fax: (410) 516-5213

Email: rhuang or huang.

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IMPORTANT DISCLAIMER

The news and other items in this newsletter are intended for

informational purposes only. Nothing in this newsletter is intended to

be a

substitute for professional medical advice.

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