Indoles for Cervical Dysplasia
Indoles for RRP
Relief from Fibromyalgia with Dietary Indoles
Indoles for Breast Cancer Prevention

Pain Relief Without Side Effects
by G. Merrill Andrus, Ph.D.
Why does the body hurt?

Much chronic pain is caused by swelling. The inflammation of joints, muscles, tendons and other parts of the musculoskeletal apparatus of the body presses on the nerves and we feel the hurt. This inflammation can come from loss of lubricity in various parts of the body for any reason.

For example, the 150 or so bursas in the body are tiny sacs of fluid that fit in where the muscles and tendons move over the bones or other muscles. They are meant to prevent wear and tear, pain and suffering. When one of these little sacs becomes inflamed, and swells up then there certainly can be pain and suffering. It doesn’t go away soon. There is need for help in dampening or eliminating the pain. Depending on the location of the pain, various ways of getting rid of the cause of swollen bursa are practiced. In the meanwhile there is an intense desire to get rid of the pain, many of which are on the market.

What do people do to relieve pain?
If the pain is familiar, the sufferer might go to the chiropractor, to a hot bath, to a heating pad, or some other tried and sometimes effective procedure. A pain in the back or the neck, a pulled muscle, repetitive strain disorder, repeated cramps and a number of other pain producing conditions can send the sufferer to look through the medicine cabinet in the home or to look on the shelves of the drug store. Most people are familiar with the various products available and they will generally buy what has worked before. Often they are willing to try a new product if previous experience with other products has resulted in unsatisfactory results or in side effects.

Suppression of pain by NSAIDs
Non-steroidal anti-inflammatory drugs (NSAIDs), a general term to describe almost all over-the-counter pain remedies, function to block the production of prostaglandins, substances that act as messengers to regulate bodily responses to crisis conditions in the body. The inflammation that causes the pain is generally for the protection of the body. The pain lets us know not to continue to use the strained muscle, for example. Once we get the message, however, we want to go on with our activities. That is why we take an NSAID.

COX-1 and COX-2
The mechanism by which prostaglandins are blocked involves enzymes called cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2). By inhibiting the formation of these enzymes the prostaglandins are inhibited. The fact that prostaglandins protect the stomach and other organs form damage complicates matters for people with chronic pain. Put simply, COX-2 will inhibit the prostaglandin that causes the pain while COX-1 will protect various aspects of body health and function. A number of prescription drugs are available which will inhibit COX-2 without inhibiting COX-1.

Nexrutine™ is a natural substance, actually extracted from the leaves of Phellodendron amurense. The herbal medicine has been used in China for 1500 years for various painful conditions.

The recent publication by Dr. Maria Bell¹, now of Sioux Falls, SD, describing her clinical study of women having cervical CIN II and III (moderate to severe cervical dysplasia) who took indole-3-carbinol (I3C^TM) orally and benefited from it, calls for us to give some background information.

Lesions on the cervix cause pain and discomfort for many women. These lesions, if unattended, can lead to cervical cancer, the second leading cause of death for women in the world. Of course, the normal defenses of the body might cause these lesions to go away for reasons that are not immediately apparent. Few want to take that chance, so they get treatment when they can. A major third world health consideration is diminishing the morbidity of cervical cancer.

What Causes Cervical Dysplasia?

The human papillomavirus (HPV) has been shown to be the agent responsible for cervical dysplasia. As a matter of fact, HPV strains 16 and 18 are found to be present in virtually every case of cervical dysplasia and cervical cancer where such agents are examined.² Papillomaviruses are small unenveloped viruses found in the skin cells of many different animals including birds, reptiles and mammals, being highly specific for their respective hosts. There are over 70 known types of HPV and most of them are relatively harmless to humans. However, HPV transmitted by sexual activity can cause genital warts as well as cervical dysplasia.

An important contribution to the study of cervical dysplasia was made in 1994 when Jeffrey M. Arbeit and his coworkers were able to produce transgenic HPV16 mice.³ That means that Arbeit took two genes from HPV 16 virus and combined them with the normal DNA of some founder mice which with their descendents would automatically have cervical dysplasia. Using such mice Arbeit and the group working with Dr. Karen Auborn have shown that feeding these transgenic mice I3C^TM will prevent most of them from developing the cervical dysplasia and cervical cancer which otherwise would have been their fate.⁴ Even earlier Japanese workers had shown that I3C^TM will inhibit the development of spontaneous endometrial cancer in female Donryu rats.⁵

The studies with mice and rats have been very important, but the work of Dr. Bell with human subjects has been especially useful. A major conclusion of this study is: "There was a statistically significant regression of CIN in patients treated with I3C^TM orally compared with placebo."

What were Dr. Bell’s actual results?

Dr. Bell had 27 subjects, all of which had clinically observable CIN II-III, treated for 12 weeks as follows:

Results:

None of the placebo group had complete regression of CIN, although many had an expected decrease in severity over the 12 weeks.

Of the 200 mg per day group, 5 out of 8 had a reduction and 4 had a complete regression.

Of the 400-mg per day group all 9 out of 9 had a reduction in severity and 4 had complete regression.

Theranaturals continues to support research such at that of Dr. Bell. It is expected that many women suffering with conditions similar to those studied by Dr. Bell will find value in the dietary indoles as dietary supplements.

References:

1. Bell, M. C., et al., 2000, Gynecologic Oncology, 78 (2), 123-129
2. Villa, L. L., 1997, Advances in Cancer Research,, Academic Press, No. 71, 321-341
3. Arbeit, J. M., 1994, J. Virol, 68(7), 4358-4368
4. Jin, L., 1999, Cancer Research,, 59 (Aug 15), 3991-3997
5. Kojima, T., 1994, Cancer Research, 54(Mar 15), 1446-1449

During the last ten years it has been shown that dietary indoles are the single most effective treatment for RRP short of surgery.¹ RRP is an acronym for recurring respiratory papillomatosis which is also called laryngeal papillomatosis. The disease is caused by the human papilloma virus (HPV) which, when established, causes warts to grow on the vocal chords and sometimes in other regions close at hand. In extreme cases RRP can invade other parts of the respiratory system including the nasal passages and even the lungs. Some people have died when massive wart growths filled their lung passages.

RRP infects just a few thousand individuals in the USA, but those who have it are sensitive to the dangers of growths that destroy the voice and inhibit breathing by blocking the airway. Many times the people who suffer most from RRP are children. Often these children are subject to laser surgery to remove the warts from their vocal chords. It is sometimes necessary to perform this laser surgery several times per year. Some of the children using I3C ^TM CAPS have significantly decreased the number of laser surgeries necessary.

This doesn’t mean that I3C ^TM CAPS are a sure cure for RRP. They do not kill the virus, as far as is known. A certain percentage of people have estradiol metabolism which is unaffected by treatment with indoles. The point is that some people are benefitted by I3C^TM CAPS as shown by two publications by Dr. Rosen of the University of Pittsburgh and his colleagues.^2,3

Why do dietary indoles inhibit the growth of warts in soft tissue like the vocal chords? Warts represent unwanted cell division and cell division results under the influence of estrogenic hormones. The dietary indoles modify the metabolism of hormones to make them less estrogenic. (For more detail on estrogen matabolism, see section on breast cancer prevention)

The understanding of how and why I3C^TM CAPS will be effective for RRP has been greatly enhanced by workers in the New York area. Over ten years ago workers at the Long Island Jewish Medical Center were working on the connection between HVP and various diseases. One especially important paper in 1993 established the connection between the metabolism of estradiol and the effectiveness of I3C^TM in the treatment of laryngeal warts.⁴

Since that time almost everyone with RRP has heard of I3C^TM and some papers have been written to the effect that this could be the treatment of choice for many people.

One of the consequences of hundreds of people using I3C^TM CAPS regularly for year after year is the affirmation of the safety of I3C^TM.

References:

1. Neuberger, C. J., 2000, RRP Newsletter, RRP Foundation, SUmmer 2000, p 7 and previous issues
2. Coll, D. A., et al., 1997, AM. J. Otolaryngology,, 18 (4), 283-285
3. Rosen, C. A., et al., 1998, Otolaryngol Head Neck Surg., 118(6), 810-815
4. Newfield, L., 1993, Anticancer Res.,, 13, 337-342

Many people with fibromyalgia may benefit from ingestion of dietary indoles, specifically indole-3-carbinol. Preliminary tests were performed simply by supplying capsules of the dietary supplement I3C™ CAPS to people reporting fibromyagia symptoms. An effort was made to contact those who received the capsules within six months of their being supplied. Over half of the patients who reported taking these capsules reported improvement in their condition.

Fibromyalgia, which afflicts approximately 2% of the women in the United States manifests itself as muscle aches and tenderness. Those who suffer from this ailment are somewhere between 10:1 and 20:1 women, as compared to men. Fibromyalgia is often associated with chronic fatigue syndrome, although there is not complete overlap of these two complaints. The cause is as yet undetermined and no general cure is known. People suffering from fibromyalgia experience different degrees of discomfort and disability as a result of the affliction.

In our preliminary tests 49 people, men and women, were given 10 day supplies of I3C® CAPS with the opportunity to purchase more if they so desired. Of this number 36 were found to have taken the capsules at a dosage of 200 to 400 milligrams daily. The remaining 13 either did not take the capsules or were difficult to contact within six months of the start of the preliminary test period.

Of the 36 people for whom data was obtained, 21 (58%) reported positive results in that their pain was reduced. These results varied from one person to another.

One person said, "I take them all the time; I am afraid to get off."

Another: "Eliminated most of the pain."

Another: "Less fatigue, hardly any aches, reduced muscle pain, better able to handle busy life."

Another: "Helps with pain. Sense of well being when she wake up in the morning. Tolerates exercise better."

Another: "90% reduction of pain, overall healthy feeling, less headaches."

Another: "Muscles are not as tender and sore."

Another: "Pain has been reduced and now seems manageable."

Others were less emphatic about the benefit. Two people (6%) were not sure whether or not they had relief. Thirteen (36%) of the respondents reported no benefits noticeable.

What are dietary indoles? When cabbage, broccoli, Brussels sprouts, and other cruciferous vegetables are macerated enzymatic reactions produce indole-3-carbinol, a reactive substance. The indole-3-carbinol might react with ascorbic acid (vitamin C) to produce ascorbigen. In the presence of stomach acid, head, or light indole-3-carbinol reacts with itself to form as many as 30 or 40 indole compounds, only a few of which have been identified.

These indole compounds, mostly indole-3-carbinol and ascorbigen, have been studied as dietary supplements for over 25 years. It is well established that at least some of the dietary indoles, when fed to laboratory animals or to humans will cause the body to alter the metabolism of estradiol, a primary female sex hormone. It has been established that about 60% of the female population respond to dietary indoles in this manner. This change in the estradiol metabolism is believed to result in a reduction of a propensity to develop breast cancer, cervical cancer, colon cancer, and other similar cancers.

It has been further observed that people suffering from laryngeal papillomatosis, a wart on the vocal chords, will experience beneficial effects from taking dietary indoles. Again about 60% of the people who have this rare disease see some benefit from taking dietary indoles.

Why people with fibromyalgia show a benefit from diet supplementation with dietary indoles is not known. This is new. But it is safe when taken as directed, as indicated by the hundreds of people taking dietary indoles for laryngeal papillomatosis (see the next article). The surprising and merciful improvement in some of those who suffer shows that this mode of dietary supplementation ought to be investigated further.

Talk with your physician before launching on any dietary supplement program for help with an ailment.

Prevention of any kind of cancer invites consideration and action by almost all humans. Yet, how can any test be devised to prove, "yes" or "no" that any given modality will definitely keep cancer from setting in. The whole human race is alert for indications that cancer can be prevented.

Attention was first drawn indirectly to I3C^TM through the observation that during the Second World War there was a dramatic drop in breast cancer among the women of Europe. One of the possibilities explored was that the diet of European women at that time included larger amounts of cruciferous vegetables (cabbage, broccoli, etc.) than before or after the War. It was also observed that the women of China and Japan consume more cruciferous vegetables than American women, and they have less breast cancer—until they move to America and adopt the American diet. Careful investigation has led to a conclusion that important benefits of eating these vegetables center around a set of chemical compounds called dietary indoles, derived from the reactions of I3C^TM in the digestive system.

As a consequence of these observations dozens of papers have been published showing that mice and other animals dosed with breast cancer and other cancers (including cervical cancer and endometrial cancer) will resist those diseases when they are fed I3C^TM. In this article we will review just a few of these studies.

A great deal of credit is due to Professor Lee W. Wattenberg of the University of Minnesota. By 1976 Professor Wattenburg and his coworkers were at the point of screening numerous plant derived nutirents as inhibitors of carcinogenesis. Their technique was to dose mice with known cancer causing materials and then feed them the natural products. By that time they recognized that the dietary indoles might be numbered among cancer inhibitors, the testing of which was reported.¹ At that time they favored the idea that these nutrients fought cancer by being antioxidants, but the conceded that other mechanisms might be possible.

Two years later the same group published positive results showing that dietary indoles fed to rats inhibited the development of a hydrocarbon-induced cancer.² During the more than two decades which have followed many researchers performed similar experiments with various cancer agents and various animals. It has become apparent that I3C^TM is effective against breast cancer tissue cultures and breast cancer in animals. The information developed is sufficiently convincing that many people are now taking I3C^TM CAPS for cancer prevention among other benefits of proper estrogen metabolism.

This action of I3C^TM CAPS involves a change in the metabolism of estradiol, the major female hormone. A urinalysis test has been developed by Michnovicz, Bradlow and their colleagues,^3,4 showing that I3C^TM will change this estradiol metabolism. When estradiol is oxidized it may become 2-hydroxyestrone or 16a-hydroxyestrone. Many studies have led to the conclusions that cancer development and growth and HPV develoment and growth are greatly augmented by 16a-hydroxyestrone, while 2-hydroxyestrone will suppress cancer development and HPV growth in many people.⁵ The urinalysis test of Michnovicz and Bradlow proves that I3C^TM, and more specifically the indole compounds to which I3C^TM is transformed in the body, substantially increases the amount of 2-hydroxyestrone resulting from the oxidation of estradiol and at the same time diminish the amount of 16a-hydroxyestrone produced. Th is change in the ratio of estradiol oxidation products appears to be very important in a number health condtions.

More recently workers at the University of California, Berkeley have shown that I3C^TM also inhibits the development of breast cancer in tissue cultures by mechanisms other than through the modification of estrogen metabolism.⁶ This study involved using I3C^TM directly on tissue cultures, rather than oral administration, indicates that there is value in the I3C^TM itself, or at least in the indole compounds to which I3C^TM is transformed in the individual cells. Furthermore, the California workers have shown that I3C^TM works synergistically with tamoxifin in combatting breast cancer already established in the cultured tissue cells.⁷

References: