THE FUTURE OF HERBAL MEDICINE IN THE UNITED STATES

Phu Patrick Le, Ph.D.
Bio-Organic Chemist
Mars 21, Incorporated
San Jose, California

Abstract

The basic differences between the "western" drugs and herbal medicines, sometimes dupped as "eastern" medicines are illustrated in typical examples. The capabilities of disease treatment of herbs are matching up with the conventional drugs and conclusions were drawn. The future of herbal medicine in the US at the doorstep of the year 2000 will be discussed in the context of what has been recently found in the domain of plant gene-alterations and what will happen next in this increasingly attractive field of herbal medicine: "Banana Vaccines" ( eating a banana which is genetically engineered to carry the self-produced vaccinating antigens) will soon replace the current painful vaccine injections that are currently administered to crying children

Introduction

The Fall of 1996 has seen a bountiful harvest of fascinating information for those of us who passion in herbal medicine. Top world authorities in the field collaborated to present the comprehensive Symposium on European Phytomedicines at the American Chemical Societyís late-August meeting in Orlando, Florida. It was a rare opportunity to hear the scientists who had actually developed herbal products discuss their findings, especially the effectiveness of the herbs involved and the important issue of their safety in human use. In the US, where not as many researches were carried out on herbs, this field could see increasing interest in the future, especially when it is combined with the relatively recent discoveries on gene splicing technique in plants and animals. We now believe that herbs can complement western medicines in numerous disease treatments, provided that they are thoroughfully studied in terms of their biochemical contents, the medical effects of each of their components, and the collective effect of the herb in use as a whole. It is this concomitant effect that makes the herbs work in situations where western medicines failed to yield satisfactory results. My paper will first go into the basic differences between conventional drugs and herbal medicines. These diferences will be illustrated by typical examples. The body portion of the paper will be dealing with a very common health problem in the US namely depressive disorder and a domain that herbs are the most helpful in, the building-up of the human immune system. The last part of the paper will discuss the future of herbal medicine, where it stands at the door step of the 21st century, 3-4 years from now.

Differential principles between conventional drugs and herbal medicines:

1. Inseparable nature of body and mind: herbal medicine physicians can not treat the visible symptoms alone but must quite often go to the roots of the disease

2. Individualized: Enlist the patient as a central figure in the healing process: The same disease described in western medicine may have different pathophysiological patterns in different individuals or in the same individual during its different stages of development requiring different therapeutic approaches, therefore herbal medicine is akin to but different from nutritional and pharmacotherapy of conventional medicine, requiring matching of therapeutic principles with meticulous diagnosis of pathophysiological pattern

3. Focus on the enhancement of the bodyís endogenous resistance: The key is to build up both the mental and physical states of the mind and body to fend off diseases: Regular taking of particular herbal medicines to enforce the body immune system. Health-cultivating lifestyle and practices (eg diet, mental & physical exercises that enhance the body and mind): Tai Chi or Meditation such as Mindful living technique of Venerable Nhat-Hanh. These practices are to maximize wellness and prevent diseases without respect to specific etiology.

4. Long term effect: Emphasis is on bodyís resistance and durability with cumulative effects built up over a long period of time: Treatment using herbal medicine are slow but have a long term effect. The actions of many herbs can be compared to a tap on the shoulder, whereas the effects of drugs can be compared to a kick in the pants. In some cases, the body will take longer to heal itself with herbs than it would with quick-acting drugs, but the long-term result is much deeper healing

5. Side-effects are minimized: A potent drug can be right on the mark when it comes to resolving certain probem, but quite often it may generate side effects or new problems. The Food and Drug Administration, which regulates the sale of drugs and approves new ones, receive more than 10,000 reports of side effects from newly approved drugs every year, according to the Center for Drug Evaluation and Research in Rockville, Maryland. This is especially alarming when you consider that about 25% of these side effects resulted in someone being hospitalized or dying. Well studied herbs produce few side effects, and many of them contain protective compounds that keep their potency in check. For example, the herb meadowsweet, which contains natural aspirin (salicylic acid), is a typical example: As you probably know, a big problem with taking chemical aspirin is that it can injure the stomach and in worst situations cause bleeding. Meadowsweet can replace aspirin to ease the pain and inflammation like aspirin but it also contains astringent tannins and soothing mucilage, which researchers believe to be compounds that buffer salicylic acid Ďs adverse side effects

6. Complex multicomponent effects: Each herb contains hundreds of active compounds, many of which act "synergistically". That means that all these compounds somehow combine to produce a greater effect than each has alone, and that the body extracts the compounds it needs and discard the others. One possible reason that scientific studies sometimes fail to confirm an herbís traditional use in healing is that the studies often focus only on the isolated compound, not on the whole plant. Each herb should be thoroughfully studied in terms of their biological contents, the medical activities of each of their components and the collective effect of the herb in use as whole. It is this concomittant effect that makes the herb work in situations where western medicines failed to yield satisfactory results.

Financial driving force is behind the big pharmaceutical companies to not properly invest enough money into the studies on herbs: Although 80% of conventional drugs are based on plants and herbs, researchers from pharmaceutical companies only focus on the active ingredient that derived from herbs and whenever possible try to mass produce it synthetically in their laboratories so they can patent the drug and get more profit out of it. If their studies revealed that such and such crude extracts from certain herb or plant can cure a particular disease, it would be much more difficult for them to patent their discoveries and common sense would dictate everyone to look for the herb which can cure the disease rather to go out to pharmacies to buy drugs

Years ago, researchers extracted an active compound called silymarin from the herb milk thistle and turn into a pharmaceutical drug to treat liver damage. Only later did German scientists discover yet another compound in milk thistle--betaine hydrochroride--that is equally important. The popular immunity-enhancing herb echinacea is another example. For many years, complex carbohydrates from echineacea were thought to be a sole active component and were extracted to produce a drug. But later on, a team of German scientists led by Dr. Wagner found out that echinacea contains other compouds that enhance immunity. Ginkgo is yet a better example: this herb which has been found to boost brain function and circulation, has been found to be much more effective when used in its whole form instead of its isolated active compounds. This illustrates the aforementioned concommitant or cocktail effect of herbs

7. Alternative solution: Provide possibilities of treatment in situations where western medical diagnosis and treatment are elusive

Depressive disorders: Major Depression or moderate to mild depression Major depression:

Diagnosis Criteria: Loss of interest/pleasure or depressed mood PLUS four or more of the following during the same two-week period: SIG: ECAPS

S LEEP: usually decreased (initial, middle-of night insomnia, or early AM awakening)

I NTEREST: marked reduction (hobbies, social life, sex drive)

G UILT: excessive rumination re past misdeeds, feelings of worthlessness

E NERGY: decreased "get up and go", fatigue

C ONCENTRATION: decreased ability to attend, think or make decisions

A PPETITE: usually decreased, with possible weight loss, but may be increased

P SYCHOMOTOR: increased (agitation, hand wringing) or decreased (eg slow speech)

S UICIDE: either passive ("OK if something bad happened to me") or active

Epidemiology and natural history:

Point prevalence of 6%-10% population

Lifetime risk of 15%-25%

Evaluation:

R/O Organic Mood Disorders: Medications eg beta blockers, corticosteroids, reserpine, alpha methyldopa, anti-epileptics, some chemotherapies. Drug withdrawal eg narccotics, eg amphe- tamines, cocaine. Infection eg tertiary syphilis, AIDS. Endocrine, eg Cushingís, hypo and hyperthyroidism, adrenal insufficiency, hyperparathyroidism. Neurologic eg Multiple Sclerosis, Parkinsonís, post-stroke (especially frontal) head trauma, dementia, sleep apnea. Nutrional eg vitamin deficiencies (B12, folate, niacin, thiamine). Neoplastic, eg pancreatic cancer

Treatment:

A two prongs approach: Psychotherapy and antidepressant medications must go hands in hands. Medications are crucial to quickly restore some very basic sense of reasoning which is usually lost in majorly depressed patients. After that, psychotherapy is the prevalent way of treatment. If patient is an adult, which is true in most cases, religious and spiritual belief or rational thinking on the meaning of life is truly a healing process, along with other practices of meditations or mindfulness living. The capacity for insight,( look into oneself), psychological mindedness and a stable environment & support from family members are critical factors in predicting the success of the treatment

Principles of Pharmacotherapy:

60%-80% of patients will respond to antidepressant treatment. There is no evidence that any one antidepressant is really surpassing others in Major Depression. Therefore, side effects generally determine the choice of medication. If one antidepressant is ineffective,another may be of value (binding sites of drug differ from one patient to the other), thus even an antidepressant within the same categories can make a difference. In some instances, one of a different biochemical profile is selected.

Dose sensibility: Very important criteria, doses are to be" fine-tuned" to therapeutic levels without causing side effects. With many drugs, surpassing that level will not cure the patients because side effects prevail over their active effects and a drug in use is dropped but in reality it may be the best drug of choice for the patient.

Do not expect remission for 3-6 weeks, though some improvement in symptoms may become evident before that time period.

Selective Seretonergic Reuptake Inhibitors (SSRIs):

It is believed that our brain needs a certain amount of "feel good" amines such as serotonin circulating around to keep us "happy". In severely depressed patients, serotonin is not produced enough or "got stuck" in brain cells. SSRIs are to inhibit such process

SSRIs are the first antidepressants to try : No cardiac toxicity, thus safe in case of overdose but numerous side effects: sexual dysfunction, headache, nausea, insomnia/hypersomnia, jitteriness, increased blood levels of some hepatically-metabolized drugs (eg tricyclic antidepressants, carbamazepine); switch to mania

These side effects are very dose sensitive. For example with such a drug like Paxil, for which the recommended therapeutic dose is a minimum of 20mg can produce enough side effects for the drug to be dropped, but a dose of 15mg may cure the patient without adverse effects which cause the drug to be abandoned in the first place, while indeed it is the drug of choice for that patient

SSRIs:

Fluoxetine (Prozac): Starting dose: 10mg. Target dose: 10-40mg mg. Advantages: long half-life, thus good in patients with poor compliance or for 1-2x/wk dosing

Sertraline (Zoloft): Starting dose: 25mg . Target dose: 50-200mg . Advantages: short half-life, thus good for short holidays for sexual functioning; flexible dosing due to pill preparation

Paroxetine (Paxil): Starting dose: 10mg. Target dose: 20-50mg . Advantages: somewhat more sedating than other SSRIs due to mild anticholinergic effect

Tricyclic antidepressants:

Work well in many patients but with cardiac toxicity: Arrythmogenic at high doses (check EKG on anyone over 40), thus often lethal in overdose. It is a no no in patients with history of cardiac problems eg arrythmia or atrial fibrillation. Numerous side-effects: Anticholinergic (constipation, dry mouth, confusion, tachycardia), tertiary amines > secondary amines. Orthostasis; weight gain.Tertiary amines include: Amitriptyline (Elavil); Doxepin (Sinequan); Imipramine (Tofranil) Cloripramine (Anafril). Secondary amines comprise: Nortriptyline (Pamelor); Desipramine (Norpramin)

MAO inhibitors: Another enzyme in the brain that also can destroy other "feel good" amines such as epinephrine or dopamine is MAO ( mono amine oxidase). MAO inhibitors are to stop that process. MAO inhibitors are usually reserved for multiply-refractory patients, have hypertensive reaction with tyramine-containing foods or sympathomimetics. Combined use with SSRIs or meperidine is contraindicated. Side-effects include orthostasis, insomnia or hypersomnia, sexual disfunction, weight gain. Even more dangerous with cardiac patients. MAOs are Phenelzine (Nardil), Tranylcypromine (Parnate)

Adjunctive medication:

Two schools of different opinions: Adding Tricyclics or Benzodiazepines to SSRIs: Klonopin is longer acting, therefore is highly recommended than Ativan. Dosage: 0.5-1mg bid along with the SSRIs. The Harvard School of Medicine recommends Tricyclics while a study from Louisiana State School of Medicine favors Benzodiazepines. Adding benzodiazepines to SSRIs not only enhance the activity of the antidepressants but also very much reduce the side-effects like jitteriness or palpitations due to the calming effects of benzodiazepines

Moderate to mild depression:

Severe depression is often succesfully treated with quick-acting synthetic prescription drugs. They may produce more-or-less unpleasant side effects, but can produce dramatic relief from depressive symptoms. Moderate to mild depression, in which symptoms do not interfere with daily activities, is actually more prevalent. In Germany, the most popular prescription drug of any type, natural or synthetic, for the treatment of mild depression is a concentrated extract of the flowers and leaves of Saint-Johnís-wort, often simply called hypericum. Many clinical trials show Saint-Johnís-wort to be especially useful in treating mild to moderate depressives states. Studies in a batch of 3250 patients found improvement or total freedom from symptoms in about 80% of the cases treated, with only less than 15% not responding.

Inside The Herb

The herbís multiple components apparently work in several different ways, one of which is MAO inhibition (aforementionned with the synthetic antidepressants). A red pigment (hypericin) found in the herb has been shown to be the active ingredient of the MAO inhibition process. MAO inhibition, however, is not the only effect found in Saint-Johnís-wort. Other components in the herb also inhibit COMT (catechol-O-Methyltransferase), another enzyme capable of destroying "feel good" amines. Still another mechanism seems to suppress interleukin-6 release, affecting mood through neurohormonal pathways.

Alternative treatment for moderate to mild depression:

This Saint-Johnís-wort can be used as alternative treatment instead of synthetic antidepressant. This herb extract dupped as the "happy tonic" is even better in these forms of depression because of its almost non existent side effect (although taking too concentrated extracts can have a slight effect on severe cardiac patients, so precautious measures dictate that EKG be taken and follow-up be carried out on these patients). Patients with major depression after coming out of the severe stage, can be switched to this herbal extract as a long-term maintenance against recurrence of their episode

The Immune System:

We have talked about how to cure some diseases with drugs and herbs; how about ways to prevent any diseases to get to us at all so we do not need to have them cured in the first place. How those monks who live way up high in the Himalaya mountains. away from any medical facility. could survive and conduct not only a healthy but also abnormally lenghthy life; some of them live way beyond the 90 years mark. The villagers in the remote areas of the countryside in Vietnam are in no diffrent conditions. The key is they all rely on their own immune system which is built up over the years to fend off diseases. I will go into ways that they use to do just that.

You may argue that they do have a different way of life than we, the big city dwellers, have. It only is a partial truth: we can always reduce our stress from our" fast-lane living styles" by practicing inner thinkings and meditations, but it seems that alone would still place us much behind those people in terms of health and joy.

This is where the herbal medicine can help you the most. The secret is you have to slowly but surely build up your immune system through years with certain herbal medicines

Echinacea--The king of immune herbs:

The most popular immune herb is echinacea: more than 300 echinacea products are being sold worldwide. The scientific studies on echinacea began in the 1950s in Germany. They have shown that echinacea can be used to improve the immune system in numerous ways. These include increasing activity of three of the immune systemís soldiers--T--cells, interferon and natural killer cells. Eschinacea also destroys many types of viruses and bacteria. Eschinacea even makes cells stronger and therefore more resistant to invasion.

Research from Germany shows that it works best as preventive medicine if you do not use it continuously. For example, you might take it for two weeks, then drop it for a week, then take it again for the next two weeks. It also is best in taking small doses (up to a dropperful of tincture, or two pills) taken several a day rather than all at once. Eschinacea is not toxic, and can be taken continously if you are fighting an active infection.The roots and seeds of this herb have the strongest immune properties, but the leaves are also fairly potent, so the entire plant can be used as well. In a relatively recent study conducted in China in 1990, even people who are perfectly healthy found that echinacea temporarily increased their immune response, by raising their levels of interferon. Ichinacea is often used in China with the herb ligustrum in an immune restorative therapy called fuzhung. This treatment has been known to increase the manufacture of immune cells in the bone marrow .

Siberian and Indian ginseng are also known as immunity enhancers. Siberian ginseng was not widely used in Russia until the 1960s, when Professor Itskovity Brekhman began studying it. This herb proved to be amazingly versatile, and soon after Brekhmanís studies, Siberian ginseng was taken into space with cosmonauts and to Olympic games with athletes. In time, its use spread to the general population of the Soviet Union. Indian ginsen has almost the same property. A cocktail of herbs combining the effects of calendula, chamomile, burdock, baptisia, red clover and marshmallow called Reizkorpertherapie have immune-enhancing properties similar to those of echinacea

All of these herbs increase immune system response and decrease the number of cancerous cells. The herb Burdock for example, has been widely use to inhibit and slow down the growth of cancerous tumors. Other herbs or herbal compounds that have pronounced effects on the immune system include garlic, shiitake mushrooms and gamma linoleic acid, which is found in evening primrose oil. Garlic has shown to slow down the growth of cancer related to the digestive tract.

Green Tea:

One very simple herb, of which numerous health benefits have been proven but very much ignored, is green tea. It guards us against various types of cancers among them are cancers of the kidneys and bladder, cancers of the upper and lower digestive tracts. Wei Zheng, MD, PhD, assistant professor at the University of Minnesota, analyzed the tea-drinking habits of 35,000 postmenopausal Iowa women and looked at which women were found to have cancer over an 8-year period. Women who drank two or more cups of tea a day --almost 10% of the overall group-were 60% less at risk from cancers of the kidneys and bladder. They also suffered one third fewer cancers of the upper and lower digestive tracts, including the esophagus and colon. To top this, women who drank four or more cups a day were even less prone to these cancers.

Studies already indicated that polyphenols found in green tea act as antioxidants that capture free radicals attacking cells. Others researchers have also found that polyphenols inhibit formations of carcinogens related to cancers in the upper digestive system, These compunds may also help to activate some enzymes that are responsible for the reduction of the bodyís exposure to carcinogens. Therefore drinking green tea is much more beneficial than drinking black tea. The reason is that the fermentation process which turns tea black would harm the useful ingredients contained in the tea leaf due to the oxidations that render them ineffective.

This explains why many Vietnamese villagers are acquiring protection against many formrs of cancers just by drinking concentrated green tea. Green tea drinking also guards them against throat and gum infections and gives them a healthy dental sructure.This so easy to get and use material is much better than those products from the pharmaceutical companies labelled as antioxidant scavengers. Fortunately, green tea is finding back its way into the US population

Finally, I have to emphasize the role of the psychologic state, meaning the balance of body and mind is very crucial to keep your immune system in check. Keeping high spirit is half the cure of any disease! With due respect, I would propose you spend 20 minutes to 1/2 hour each day for your inner life and reflections. It will give you peace and a meaningful sense of life and tremendously help you reduce your stress and avoid diseases, since people with two much stress and worries have their immune system weakened and their body opened for disease to invade, despite any good medication they take

Conclusion:

The reality is herbal medicine is more widely used now in the western world, especially in European countries. Therefore, herbs should not be dupped as eastern medicines anylonger. The US has seen increasing use lately, especially in the field of health foods. But let me tell you where the future of herbal medicine stands in the next few years: There will be some forms of modernized herbs that replace the traditional prescription drugs that are currently in use.

I am talking about up-coming innovations in the field of pharmaceutics such as "banana vaccines": (instead of giving a shot to crying babies, a banana which contained the natural vaccines will take place); or covering your earís infection is simply done by eating some other fruit

The modern trend is gene alteration (or splicing ) of the herb and plant that leads to the natural production, either of novel medicines or more of the existing ones so extractions or isolations of the active ingredients are not neccessary, but instead direct ingestion of the fruit or the herb will be replacing pills and injections

Backgrounds: Studies so far have proven tobacco plants can be engineered to produce the hepatitis B surface antigen. The plant antigen strongly resembles that used in the current recombinant hepatitis B vaccine. Mice innoculated with leaf extracts from the plants show the full immune response seen in humans vaccinated with the hepatitis B vaccine.

Potatoes produced an antigen of enterotoxic escherichia coli responsible for numerous cases of diarrheal disease in developing countries, and mice showed immunity to the antigen after eating the raw potatoes

The basic principles of these new herbal medicines are: The plants or herbs are genetically engineered to carry genes from disease-causing microbes. Within the microbes, these genes control production of molecules, or antigens, known to provoke an immune response in those infected with the microbes. Once inside the plantís genetic DNA, the genes force the plant to produce the vaccinating antigens.

Plant molecular biologist Charles Arntzen has been working on banana vaccines since 1991. He discovered that foreign genes can be inserted into banana DNA. Arntzen and his colleagues are currently in the process of applying to FDA for authorization to conduct human trials using the "banana vaccines". According to newest releases, Arntzen and his colleagues have produced small plants with vaccine genes that are prototypes, but according to him, it wiil take 2 years for them to have the first fruit and the fruit must then be tested in animals first. So look for these banana vaccines somewhere right there in the begining of the 21st century

To conclude, there is place for rapproachment between herbal and conventiomal drug; the future of herbal medicine is there with the modern technique of gene alterations.

Gene splicing on animal and plant is relatively new since the 1980s , but it will be the gems of the future. Three and a half billions dollars have already been given to the NIH (National Institute of Health) by the federal government to map out some 100,000 different DNA of the human race. This human DNA mapping is very important in modern medicine because it will play a crucial role in predicting what kind of disease a person will be subjected to, so preventive measures can be taken in time before the disease can cripple the subjected individual. The Livermore lab will carry out most of the work and will be hiring thousands of scientists in this field of molecular biologists and biochemists. If you are looking for a future career, then look no farther!

Reading List

Books

Fundamentals of complementary and alternative medicine. (1966). Micozzi, Mark S. (Ed.).New York: Churchill Livingstone.

Oriental medicine: An illustrated guide to the Asian arts of healing. (1996). Van Alphen, Jan & Anthony Aris (Eds.). Boston: Shambhala.

Chinese Herbal Medicine, Formulas and Strategies. (1993). Bensky, D.& R. Barolet. Seattle: Eastland Press.

The Honest Herbal. (1996). Varro E. Tyler. Philadelphia: St. Martinís Press.

Journals

Ameican Journal of Chinese Medicine.

Journal of Alternative and Complementary Medicine.

American Journal of Psychiatry.

American Journal of Pharmacognosy.

Selected Articles

Eisenberg DM, Kessler RC, Foster C, Norlock FE, Calkins DR & Delbanco TL. (1993). Unconventional medicine in the United States: Prevalence, costs and patterns of use, New England Journal of Medicine 328(4):246-252.

W. John Winkelman. American Psychiatric Association practice guidelines for major depressive disorder in adults, American Journal of Psychiatry 1993; 150:1-23 (supplement).

Richards A. Cassandra (1997). Vaccine cuisine could be the wave of the future, Infectious Diseases In Children 10(1):7&40.

Brent D (1993). Depression and Suicide in Adolescents, Pediatrics in Review 14(10):380-388.

WD Nes, PH Le, et al. (1987). Synthesis and fungistatic activity of Podocarpic acid derivatives, A.C.S. Symp. Ser., 325 (Ecol. Metab. Plant Lipids): 140

WD Nes & PH Le (1990). Evidence for separate intermediates in the biosynthesis of 24-methylsterol end products by Giberrella fujikuroi, Biochim. Biophys. Acta, 1042: 119