Natural medicine: will that be a pill or a needle?
William H. Baarschers
Many alternative practitioners promise to reveal “secrets your doctor never told you.” One secret is never mentioned: why alternative remedies are ingested rather than injected. Though most practitioners of alternative medicine are silent on this question, this “missing information,” as previously described by Kardes and Sanbonmatsu (2003), is crucial for evaluating the promised cure.
So-called natural medicines, usually herbs or supplements, are invariably things to eat or drink. And why not? Ever since the appearance of pharmaceuticals in the early 1800s, the doctor’s prescription, legible only to a pharmacist, would nearly always get you something to swallow–a liquid, a pill, or a powder; an extract of senna leaves to relieve constipation, for example, or a “headache powder.” Only occasionally would the prescription get you something to rub on your skin, like a salve. Today, medication still comes mostly in pill or capsule form.
By the late 1800s, Louis Pasteur’s work with microorganisms brought about the first vaccines, for anthrax and rabies. BCG (bacillus Calmette-Guerin) vaccine against tuberculosis appeared in 1921, and by 1955, Jonas Salk developed his polio vaccine. These vaccines could not be swallowed, they had to be injected. With a needle. But inflicting pain is unpleasant and discourages parents from bringing their children for vaccination. Therefore, Albert Sabin’s 1965 oral polio vaccine was an important discovery.
The 1960s also brought the oral contraceptives–birth-control pills. Carl Djerassi, a chemistry professor at Stanford University known as “the father of the birth-control pill,” preferred to call it “chemical fertility control.” What was so special about oral polio vaccine and oral contraceptives? Did we not always swallow our medicines? Why were these oral medications such a breakthrough?
Although polio vaccine and birth-control pills are Far apart in the pharmaceutical spectrum, the reason for the importance of “oral” is the same. Research often yields promising compounds that act on microorganisms or on cell cultures in vitro, in the shallow glass vessels called petri dishes. Next, the potential remedy is tested on animals, usually via a syringe. How does it get to be a pill? Or does it?
From Needle to Pill
Progesterone is a hormone secreted during pregnancy. One of its functions is to prevent the fertilization of other egg cells. It is the natural form of birth control, but it cannot be used as a pill. Progesterone is absorbed readily through the intestinal wall and is quickly metabolized on its first pass through the liver. Its half-life in the blood stream is about five minutes (Katzung 1998). Chemically modifying the progesterone molecule avoids this problem. That modification allowed the development of the Pill.
The moment we swallow something, what we eat starts on an obstacle course toward its destination. Enzymes in saliva begin the attack. Then the strongly acidic environment in the stomach alters many food molecules. Chemicals that survive this far face the digestive enzymes on their way through the small intestine. Eventually, some useful products of the breakdown of our food are absorbed through the intestinal wall into the bloodstream. Others are fermented by the bacteria in our colon, and still others are excreted.
More hurdles wait in the bloodstream. Portal blood carries absorbed food-derived molecules first to the liver, which can metabolize a chemical, be it food or medicine, before it reaches the systemic circulation. It’s quite a steeplechase for whatever we eat.
Like the family doctor of old, alternative healers also give us pills or teas. After all, we have been conditioned to accept medicine as something we eat, never mind who recommends or prescribes it. But there is a difference between the alternative and the conventional. We invariably eat or drink the herbalist’s prescriptions. But physicians, although they prefer to prescribe pills or capsules, must sometimes reach for the needle, because many effective drugs do not cope well with the rigors of our digestive tract. A drug’s susceptibility to digestion or its poor absorption through the intestinal wall result in poor bioavailability. Such drugs must be injected to bypass the digestive system. The alternative-medicine approach rarely considers the bioavailability question.
Of an annotated list of North American prescription drugs, fully one third cannot be taken orally for these reasons (Springhouse Corporation 1996). They are injected, usually by a nurse or a doctor. In contrast, the complementary approach holds to the view that good medicine, provided by nature, comes from plants. It should be eaten, even if the extract must be sealed in a capsule. Strangely, although chemical laboratories are not kindly thought of by herb users, buying herbal extracts sealed into laboratory-made capsules does not seem to be a problem.
An early step in testing new drugs is determining how the drug reaches the target organ, how much enters the circulation, and how quickly it is metabolized or excreted. Without knowing this pharmacokinetic behavior, we cannot predict what happens after we swallow the pill, the capsule, or the tea.
A chemical called amygdalin, extracted from peach or apricot pits, was touted throughout the 1970s as an anticancer drug under the name Laetrile and became the subject of much controversy. While some alternative healers still believe Laetrile is a cancer drug, conventional medicine has rejected it. Laetrile molecules consist, in the chemical sense, of three smaller building blocks: benzaldehyde, glucose, and hydrocyanic acid. The last one is a highly toxic chemical, the “cyanide” of detective stories and gas chambers.
The reason for rejecting Laetrile is its pharmacokinetic behavior. When injected into cancer patients, it was quickly and almost completely excreted in the urine (Moertel et al. 1981). Given orally, it is rapidly split into its building blocks by stomach acid, causing elevated but nonlethal blood levels of cyanide. Since injected Laetrile is not absorbed, and if orally administered, the drug is destroyed by digestion, whatever it does to cancer cells in a lab is irrelevant.
Magic Mushrooms
Laetrile nicely illustrates the bioavailability problem with oral remedies, but there is a much more romantic example. The shiitake mushroom has an important place in both the food and the medicine of Asian countries, particularly China and Japan.
A mushroom’s overnight appearance, seemingly out of nowhere, must have seemed like pure magic to our ancestors. No wonder mushrooms have been used as both food and medicine in virtually all cultures for thousands of years. Some were just considered good treatment for common ailments. Others were powerful “medicine,” consumed by shamans in religious ceremonies (Schultes and Hofmann 1979). Hallucinogens in these mushrooms are closely related to dopamine and serotonin, chemicals directly involved in brain function.
Mushrooms are also food. The nutritional value of the shiitake is similar to that of other vegetables. It is about 90 percent water, some carbohydrates, some minerals, small amounts of vitamin C, and a little protein, although shiitake’s protein content is only half that of the oyster mushroom (Chang 1980).
A little mycology, or fungus science, helps to appreciate the shiitake story. The often-invisible, underground part of a fungus is the mycelium, or vegetative part. It grows in soil, in wood, or other organic debris. The spore-bearing fruiting bodies are the actual mushrooms. They are formed only when conditions of temperature, humidity, and the fungus’ stage of growth are just right. The shiitake belongs to the white-rot fungi, which grow on rotting wood and slowly break it down for the benefit of other forest dwellers. Mycelium of white-rot fungi, grown in culture, is used to biodegrade some food processing wastes (Vinciguerra et al. 1995). But it is the fruiting body, the actual mushroom, that goes so well with that juicy steak.
Shiitake mushrooms have played an important role in ancient Asian medicine because they contain two notable chemicals. One is reported to be an anticancer compound, and the other can lower blood cholesterol.
Mushrooms and Lemons
The reported anticancer effect of shiitake mushrooms has a prominent place in modern complementary-medicine literature. Although not always explicitly mentioned as a reason for eating the mushrooms, the suggestion is there when we see a story on the anticancer effects of shiitake illustrated with a fresh, delectable mushroom (McCaleb 1994). Other advice explicitly states that eating shiitake helps to resist tumors, whatever “resisting tumors” means (Bremness 1994). In North America, shiitakes are a tasty, luxurious companion to steak and red wine. Are they also an expensive medicine?
Shiitake mushrooms first appear in the scientific literature around the late 1960s (Maeda and Chihara 1971). The molecular structure of the isolated active compound, lentinan, was found to be that of a carbohydrate. Not very exciting–what could be more common than a carbohydrate? Nevertheless, numerous scientific reports on lentinan’s anticancer potential have appeared during the past forty years, and they continue to appear. Lentinan appears to slow tumor growth, but most experiments are with cell cultures or small numbers of animals (Suzuki et al. 1994). Lentinan does not kill cancer cells–it is not cytotoxic.
Association of carbohydrates with the surface of cells plays a role in the “recognition” tasks of those cells–an important part of our immune system. Lentinan is believed to support those immune system tasks. Consequently, such chemicals have been called “immune-response modifiers.” Similar carbohydrates are found in other mushrooms, like maitake and reishi. Chinese herbal medicines Hunang Qi (Astragalus) and Dankei (Angelica) are called immune modifiers in an American patent (Liu 1989). A carbohydrate found in ordinary wheat straw also has immune modifying properties (Nakahara et al. 1967).
There is more tempting news. Citrus pectin is also a carbohydrate, the soluble fiber we find in many fruits. News about citrus pectin in relation to prostate cancer was illustrated with a good-looking, juicy lemon (Webb 1997). The question is obvious: If forty years of research show readily available, cheap carbohydrates to be cancer-fighting and immune strengthening, why do we still not have a carbohydrate-type anticancer drug? Is the “medical establishment” missing the boat?
Cancer Drugs?
Let’s start with the mushroom. Most of the literature reports on lentinan are in Japanese scientific journals, with English summaries in Chemical Abstracts–about a thousand studies in the past thirty-five years. What a remarkable interest in a gourmet mushroom. The critical question is: How was the lentinan applied? In a random sample of a couple of hundred of these reports, about two-thirds mention the use of injections. Some patents describe “injectable solutions” (Guo and Liu 1993). The remaining reports simply stated that lab animals were “treated” with lentinan. A rare citation mentions oral application.
Lentinan is a large carbohydrate molecule that would not be absorbed through the intestinal wall. Taken by mouth, lentinan is either digested, like starch, or more likely, it is a nondigestible carbohydrate, like pectin or cellulose (Noah et al. 1998). As a dietary fiber, either it will be fermented in the colon or it will be excreted. Lentinan, if it is a drug at all, would have to be an injectable drug.
The literature regarding lemon is different. It specifically mentions that oral administration of the modified pectin inhibited the metastasis of prostate cancer in rats (Pienta et al. 1995). The citrus pectin was quite extensively modified, by way of a well-established laboratory procedure for partially breaking down the large pectin molecules into much smaller fragments, which may well be small enough to pass through the intestinal wall. What reduced metastasis in the rats was not a “complex carbohydrate” but rather a much smaller molecule. Nobody knows, as yet, what the human digestive system would do to it.
And why citrus pectin? Because it is convenient and readily available from chemical-supply companies. Pectin from any other source, like apples, could well have given similar results (Nakahara et al. 1967). The lemon connection was coincidental. Illustrating the story with a fresh lemon made it attractive, but the research had nothing to do with eating lemons. The “herbal connection” was purely symbolic.
These studies are important. This is basic research that reveals interactions of specific carbohydrates with mammalian metabolism. Carbohydrates, the primary products of photosynthesis in plants, are abundant, cheap, and renewable. Plants make them in enormous variation and in huge quantities. They are used as food and food additives and in various medical applications. At least six herbal plants with a very high content of the so-called carbohydrate hydrocolloids, like pectin, are routinely used in Europe. Since carbohydrates interact so readily with other chemicals, including enzymes, a long list of “modified” carbohydrates has been developed to serve both the food industry and medicine (Franz 1989). Anticancer drugs are not on the list.
Policy Issues
Even if lentinan has to be an injectable drug, so what? We just found that nearly a third of all prescription drugs are injectable. Unfortunately, in the case of lentinan, the injection is not a good solution for getting around the digestion problem. The size of the lentinan molecule also causes problems for the needle.
Injecting large molecules like carbohydrates or proteins directly into the bloodstream provokes the body’s defense systems. This is the basis of the rejection mechanism of transplanted organs. Large, foreign molecules are recognized by our immune system as invaders, like viruses and bacteria. Several research reports on lentinan comment on blood-vessel dilation and internal bleeding caused by the injections (Maeda et al. 1992). This is one of the reasons the American National Cancer Institute (NCI) excludes from further investigation all compounds that turn up in that organization’s screening programs and that are either carbohydrates, proteins, or tannins–the large molecules that are likely to provoke immune reactions (Cragg et al. 1995).
Not all scientific opinion agrees with NCI’s policy; investigation into the medicinal potential of carbohydrates continues in many places (Franz 1989). This work on carbohydrates is just another small battle in the “war on cancer,” and it will probably carry on for a while. But so far, the carbohydrate approach has not yielded an anticancer drug.
Cholesterol and a Juicy Steak
A further, curious wrinkle in the shiitake story has to do with another killer, heart disease. Another chemical in this fungus was found to lower blood-cholesterol levels. The chemical, initially called lentinacin, first appeared in the literature in 1969 (Chibata et al. 1969). Shortly afterward, chemists changed its name to eritadenine. It was reported to be ten times more effective in lowering blood cholesterol than clofibrate, a first-generation synthetic drug for treating hypercholesterolemia (Spoerke and Rumack 1994). However, eritadenine disappeared from the science literature around the early 1980s. Chemical Abstracts indexes of the past fifteen years no longer mention it. Perhaps that is just as well. A synthetic preparation of eritadenine would, of course, be perfectly identical to what the mushroom produces. But it would have to go through the same costly testing protocol as other drugs before it could become clinically available. That would make it much more expensive than gourmet mushrooms.
The behavior of a chemical in our digestive system and in the bloodstream is very important. For legal prescription drugs, this pharmacokinetic behavior is studied and is known. For many herbal remedies and plant extracts it is not known. It is a secret your (naturopathic) doctor never told you. Many plant extracts have useful medicinal properties, but we need to know if we have to take them as a pill or through a needle … or as a juicy steak with mushrooms.
References
Bremness, Lesley. 1994. Herbs: The Visual Guide to More than 700 Herb Species from Around the World. Toronto: Stoddart Publishers.
Chang, S.T. 1980. Mushrooms as human food. Bioscience 30(6):399-401.
Chibata, I., et al. 1969. Lentinacin: a new hypo-cholesterolemic substance in Lentinus edodes. Experientia 25(12):1237-8.
Cragg, G., et al. 1995. Pharmaceutical prospecting and the potential for pharmaceutical crops: Natural product drug discovery and development at the United States National Cancer Institute. Annals of the Missouri Botanical Gardens 82:47-53.
Franz, G. 1989. Polysaccharides in pharmacy: Current applications and future concepts. Planta Medica 55:493-7.
Guo, R., and Y. Liu. 1993. Formulations of lentinan for intravenous injection, Japanese Patent CN 1,076,112 (Chemical Abstracts, 120, 331103s).
Kardes, Frank R., and David M. Sanbonmatsu. 2003. Omission neglect: The importance of missing information. SKEPTICAL INQUIRER 27(2) (March/April):42-46.
Katzung, Bertram G., ed. 1998. Basic and Clinical Pharmacology, seventh edition. Stamford, Connecticut: Appleton & Lange.
Liu, Yagnang. 1989. Polysaccharide containing pharmaceutical composition from plants for increasing the immune function. U.S. Patent 4,843,067.
Maeda, Y.Y., and G. Chihara. 1971. Lentinan, a new immuno-accelerator of cell-mediated responses. Nature 229:634.
Maeda, Y.Y., et al. 1992. Genetic control on lentinan-induced acute phase responses and vascular responses. Folia Histochemica Cytobiologica 30(4):207-9.
McCaleb, R. 1994. Research reviews. HerbalGram 30:10-12.
Moertel, C.G., et al. 1981. Pharmacological and toxicological study of amygdalin. Journal of the American Medical Association 245(6):591-4.
Nakahara, W., et al. 1967. Inhibition of mouse sarcoma 180 by a wheat hemicellulose B preparation. Nature 216:374-5.
Noah, Lionel, et al. 1998. Digestion of carbohydrate from white beans (Phaseolus vulgaris L.) in healthy humans. Journal of Nutrition 128(6):977-985.
Pienta, K.J., et al. 1995. Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin. Journal of the National Cancer Institute 87(5):348-52.
Schultes, R.E., and A. Hofmann. 1979. Plants of the Gods, Origins of Hallucinogenic Use. New York: McGraw-Hill.
Spoerke, David G., and Barry H. Rumack, eds. 1994. Handbook of Mushroom Poisoning. Boca Raton, Florida: CRC Press, 391-9.
Springhouse Corporation. 1996. The Nurse Practitioners’ Drug Handbook. Springhouse, Pennsylvania: Springhouse Corp.
Suzuki, Manabu, et al. 1994. Antitumour and immunological activity of Lentinan in comparison with LPS. International Journal of Immunopharmacology 16(5/6):463-468.
Vinciguerra, V., et al. 1995. Correlated effects during bioconversion of waste olive waters by Lentinus edodes. Bioresources and Technology 51 (2/3):221-6.
Webb, G. 1997. Citrus pectin may inhibit metastasis of prostate cancer. HerbalGram 40:17.
William H. Baarschers is a professor emeritus of chemistry at Lakehead University in Thunder Bay, Ontario. His research interests have included the chemistry of medicinal plants, synthetic chemistry, environmental science, and industrial toxicology. He is currently advisor to the University’s Resource Centre for Occupational Health and Safety. He is the author of Eco-Facts & Eco-Fiction: Understanding the Environmental Debate (Routledge, 1996).
COPYRIGHT 2005 Committee for the Scientific Investigation of Claims of the Paranormal
COPYRIGHT 2005 Gale Group
