Food, Medicine, Poison & “Molecular Vitalism”

Novel Conceptual and Clinical Tools for the Botanical Treatment of Cancer

Patients confronting a diagnosis of advanced (stage 4) cancer face the statistical reality that conventional chemotherapy can effect a cure only a tiny minority (between 1-3% depending on the malignancy) of all such cases. More often than not, the reasonable impulse of these patients to investigate alternative treatment options such as herbal medicine is met with negative responses from oncologists. As a result, consumer-patients challenged with cancer seeking herbal medicine resources may resort to unreliable products promoted on the Internet or via multi-level-marketing which offer dubious herbal “cures”. Patients may also be less willing to disclose any use of these products to their physicians.

The emerging integrative model of cancer treatment recognizes the importance of botanical medicine. However, despite extensive positive research data from experimental and preclinical studies, and the anecdotal clinical experience of many practitioners, patients and cancer survivors, its potential in this field remains largely untapped and large-scale clinical trials are generally unavailable. The reasons for this are multifactorial, and include historical, political, and cultural factors – and almost invariably a misunderstanding of the core principles of herbal medicine itself.

An important but often overlooked distinction exists between herbal medicine, (the practice) and herbal medicines (the plant based remedies used in the practice of herbal medicine).1 The current trend of presenting so called “scientific information” about herbs divorced from the context of herbal medicine that defines their medical use is rather like presuming that knowledge of needles will

provide an understanding of acupuncture. It is only the specific discipline of herbal medicinethat enables a therapeutic understanding of medicinal herbs.2

 In Europe, herbal medicine (also known as phytotherapy) is a legally recognized healthcare delivery system, and traditional medicines are considered a distinct regulatory category. In the United States, neither herbal medicine (the practice) nor traditional herbal medicines (the remedies) are recognized as such by the legal and regulatory frameworks that determine healthcare provision and the availability of medicines for American citizens.

Herbs are regulated in the US under DSHEA(1994) as “Dietary Supplements”, as opposed to the European category “Traditional Medicines”. A traditional medicines category for herbs is important for two reasons: it legitimizes the obvious fact that herbs have medicinal value (medical claims are not allowed for “dietary supplements”) and it also asserts that valid evidence and support for efficacy and safety derives from empirical (traditional) use over many years. Traditional use evidence does not replace scientific or clinical trial data, but is a unique category of evidence, which separates herbs with many years of medicinal use from modern engineered nutraceutical products that are promoted as “natural” dietary supplements. A good example would be the traditional herb ephedra, used safely for centuries in Chinese medicine, as opposed to modern“fat burning” dietary supplements combining ephedrine alkaloids, aspirin and caffeine that were promoted as “natural” weight loss aids.

Secondly, herbal medicine as a professional practice is technically illegal in the United States, an anomaly among English speaking countries (such as England, Australia, New Zealand and Canada). This is the legacy of active political suppression in the early 1900s, by an alliance between the then recently formed American Medical Association (AMA) and emerging pharmaceutical companies. At that time there were between 30-40,000 physicians (MDs) across the US trained by the Eclectic Botanical Medicine movement who used botanical remedies as their primary method of treatment, and over 50% of the drugs listed in the United States Pharmacopoeia were botanicals. The AMA used the Rockefeller financed Flexner Report in 1910 to shut down the national network of botanical medical schools, on the pretext of inadequate laboratory facilities, particularly for anatomy.3 By 1934, there was not a single remaining botanical medical school in the US, and the percentage of botanicals in the USP had dropped from over 70% to 30%. (Today the proportion of botanical substances in the USP is <1%).4

The legacy of this suppression remains today, and herbalists who diagnose and treat medical conditions are vulnerable to the felony charge of practicing medicine without a license - in several states this has proven to be a more than theoretical concern. In some states, licensed Naturopathic Physicians (NDs) may legally prescribe and dispense herbs, and Licensed Acupuncturists (LAcs) may dispense Chinese herbal remedies. There is also a small but significant number of experienced herbal practitioners in the US, most of whom are professional members of the American Herbalists Guild (AHG). AHG professional members operate within a framework of informed consent, offering consultations about how botanicals can be used safely and effectively by their clients.

It should be noted that while many of the leading medical schools in the country have now formed “integrative medicine” departments, the faculty of these units is invariably composed of physicians lacking specific training in botanicals or herbal medicine, whilst herbalists and naturopathic physicians are conspicuously absent from the roll-call.  This is, at present, more a cosmetic exercise in response to patient pressure and prospective-student demand; at the same time various medical professionals, institutions and organizations continue to launch poorly-informed attacks on herbs and herbal medicine, often so explicitly inaccurate that their political motivation is transparent. Last, but far from least, the international pharmaceutical corporations have extended their quest for profits to influence every level of modern healthcare, from so called “peer-reviewed” journal studies through to consumer ads for prescription drugs on cable TV. Pharmaceutical companies have little interest in herbal medicines, because plants are not inherently patentable, and freely available to all. The resultant effect of these various historical cultural political and economic factors is that the real principles of herbal medicine are not well-known, known, yet at the same time its tools, plant medicines, are subject to extensive misrepresentation and negative publicity.

Food as Medicine - Medicine as Food: Hippocrates

The principles underlying herbal medicine are relatively simple, but are quite distinct from those of conventional medicine. They start from the common sense view, originating in prehistory and still universal among indigenous cultures, about how to classify the different substances that humans ingest, based upon how the body responds or uses them. Accordingly, everything we consume falls into three broad groups: - food, medicine and poison.

Food, Medicine and Poison are distinct yet overlapping categories

Food and Medicine are Interrelated

Food, Medicine & Poison: Physiomedicalism

The leading practitioners and theorists of Physiomedicalist herbalism formulated the clearest statements about the nature of food, medicine and poison over 100 years ago. Thurston and Lyle developed a systematic vitalist philosophy that clearly differentiated between these materials, and in particular identified ‘poison” with the drug therapeutics of the medical “regulars” (= pharmaceutical) biomedicine.1, 2

Foods are complex, contain many different constituents, and furnish materials that are used by the body to nourish, support and reproduce its vital activities. The body “acts” upon foods, through digestion and assimilation to produce and reproduce itself; for maintenance; sanitation; and repair and renewal. Food and medicine are thus theoretically and in practice closely connected and functionally overlapping categories. For the physiomedicalists, the body acts upon both medicine and food. Both these agents are “passive” although they have they capacity to influence by providing material support for the vital force. This is in contrast to poison which is active and destructive.

Thurston emphasizes that these distinctions, although at first sight subtle, are far from semantic. To clarify by an example, the question often demanded by mainstream clinical trials is whether a given herb “works” or not. But no one asks whether scrambled egg “works”. It is an obviously meaningless question.. This is the real explanation of why for example clinical trials on “echinacea for colds” or “St. John’s Wort for depression” continue to generate inconclusive data despite endless methodological variations in study design. Yet the “evidence based herbalism” tendency has conspicuously avoided addressing the issue of how best to study herbal influence on the vital force, maintaining that herbal efficacy must be measured in drug terms.

A Note on Poison

When a poison is ingested, it acts in a harmful way upon the structure-function of cells, tissues or organ systems of the body. This is the fundamental difference between medicine and poison. While the body acts on food, (and medicine poison acts on (harms) the body, actively disrupting the vital processes, interfering, interrupting, impairing, in a dynamic manner in contrast to the restorative, curative and yet passive influences of medicine.

Although it is often said that the dose makes the poison, which may be relatively true, it is also the case that true medicines, according to the physiomedical definition, are categorically distinct from poison. The one is inherently curative, and the other is inherently destructive. The physiomedicalists were distinguished by their insistence on gentle plant remedies, unlike the Eclectic physicians who used more toxic botanicals in appropriate doses but nonetheless with a drug-like approach to their specific indications.

Certain plants have furnished modern medicine with drugs that are used in cancer therapy as cytotoxic agents. The better-known examples of these are Taxol, from the Pacific yew tree, and the vinca alkaloids from the Madagascar periwinkle. These compounds, unlike the chemopreventive compounds described below, are effective as anti-cancer agents by virtue of their nature as poisons which disrupt the cell cycle. Their destructive nature as poisons is clear. However the fact that plants were the original source of some pharmaceuticals – the classic example being Withering’s use of foxglove for dropsy and the cardiac glycosides – can blur the distinctions between two very different kinds of agents - medicines and poisons.

Finally, although the simplistic model of food medicine and poison may have worked well both for our ancestors and for indigenous peoples today, it has become seriously distorted in our advanced industrial societies. Poisons are ubiquitous, in the environment and food chain, and are detectable in large numbers in our bodies.9 Meanwhile, food, or at least much of what is sold as “food” can arguably be categorized as poison in terms of its industrial processing, synthetic additives, colorings and preservatives, pesticide residues, and a nutrient composition emphasizing “bad” fats and simple sugars and lacking in beneficial minerals, vitamins and phytonutrients. At the same time, regular medicines, that is modern pharmaceutical drugs, have become a major killer and are quite properly defined as poison, and a leading cause of death among US citizens.3

Chemoprevention

Chemopreventive foods become chemotherapeutic botanical medicine

Common Chemopreventive Dietary Compounds

Pharmacological Multitasking

Chemopreventive plant compounds affect all phases of the cancer process, i.e., tumor initiation, promotion and progression. Botanical medicines are complex natural mixtures of pharmacological multitaskers, simultaneously exerting influence on different levels and via different mechanisms.5 By contrast, pharmaceutical drugs are classically single synthetic compounds, ideally interfering or disrupting a single specific mechanism, whilst minimizing collateral damage (AKA side effects). As dietary or food ingredients these chemopreventive compounds assist the stabilization, arrest and even reversal of cancer.

Botanical Compounds target all three phases of the cancer process

Basic science research is confirming that many chemopreventive dietary compounds are active at precisely the molecular targets that drug designers seek to affect with the newer generation “targeted” drugs, typically the monoclonal antibody (MCA) agents.10,11 Despite massive investment and effort, only a handful of such drugs have been licensed to date – such as Iressa, Gleevec, Herceptin Avastin, Tarceva and others. Yet chemopreventive plant compounds have been shown to engage the very same molecular targets that have been identified by cancer research scientists attempting to formulate these “smart drugs”. With an established safety record and a fraction of the cost of conventional chemotherapy, plant compounds represent an enormous and almost untapped resource for cancer treatment. Almost every article in the basic research literature concludes by suggesting that chemopreventive plant compound are potentially a hugely important therapeutic breakthrough for cancer treatment. These compounds affect all phases of cancer.

Of these, probably only Herceptin is the only drug that has proven itself of significant benefit, yet it is expoesnove enough that Her/2 neu positive breast cancer patients in England are not routinely given the drug due to its cost.

Molecular Processes of Cancer Influenced by Chemopreventive Compounds

Immunomodulation

Another key role for plant medicines in cancer is immunomodulation. A common misconception among lay people is the oversimplified idea that “stimulating the immune system” will eradicate a cancer. In fact, cancer evades immune system surveillance because of the low immunogenicity of most tumors. Nonetheless, many patients with advanced malignancy do have lowered levels of innate (Th1) immunity, the branch of the immune system whose cells, such as natural killer (NK) cells, directly kill tumor cells. A variety of herbal medicines and plant compounds directly stimulate this innate immune response. (These same agents can be used to help protect bone marrow against the myelosuppressive effects of conventional chemotherapy.) The two most important classes of herbs in this group are the immunomodulating medicinal mushrooms such as Shiitake, Maitake and Reishi, and the adaptogens including Panax ginseng, Eleutherococcus, Rhodiola, and others.

The capacity of the mushroom polysaccharides to influence the level of immune function can be regarded as a direct expression of the way in which botanicals enhance the vital force. Similarly adaptogenic herbs enhance the capacity to respond to increases in allostatic load by multiple pathways particularly involving the hypothalamic-pituitary-adrenal axis. This is too is clearly an effect mediated by the vital force as opposed to a drug based anti-disease “action”.

Immunomodulating and Adaptogenic Botanicals Lack Drug Equivalents

In both cases, we see that the plant medicines have no equivalent among pharmaceutical drugs. The mushrooms polysaccharides are not only immunostimulatory, but are also “pharmacological multitaskers” when it comes to their effects on cancer progression. The adaptogenic herbs such as Panax ginseng are also without equivalent in the pharmaceutical drug domain : they are non-specific, non-toxic, and “normalizing”. This means the effect they produce varies according to the physiopathological state. For example, ginseng is an angiogenic in wound healing. Versus cancer, the same herb is antiangiogenic.12 Finally adaptogens can have a range of beneficial interactions with conventional chemotherapy and radiation.

Patients confronting a diagnosis of advanced (stage 4) cancer face the statistical reality that conventional chemotherapy can effect a cure only a tiny minority (between 1-3% depending on the malignancy) of all such cases. The developing integrative models of cancer care are in part driven by these statistics. Such models recognize the multifaceted nature of the cancer process and combine multiple treatment modalities, from spiritual and mind-body interventions to biologic and physical therapies, while also differentiating healing from cure. The integrative model of cancer treatment depends in large part upon of botanical medicine. However, despite extensive positive research data from experimental and preclinical studies, and the anecdotal clinical experience of many practitioners, patients and cancer survivors, its potential in this field remains largely untapped and large-scale clinical trials are generally unavailable. The reasons for this are multifactorial, and include historical, political, and cultural factors – and almost invariably a misunderstanding of the core principles of herbal medicine itself. This can be clearly seen in clinical trials which attempt to use the models derived from cytotoxic chemotherapies (phase 1-3 TRIALS) and apply the m to dietary compounds. (REF green tea etc)

Advanced cancer is a multifactorial process which demands multifactorial treatment. Integrative strategies for metastatic disease may vary in detail but a working multiphase model is shown below (the phases are may overlap in practice).

A Multiphase Treatment Strategy for Advanced (metastatic) Cancer

The areas where botanical medicines are most effective are shaded (Phase 2, 3, 5 & 6 in the chart). Tumor cytoreduction or debulking (Phase1) is best effected by conventional surgery or other physical means, or conventional chemotherapy (which should be assay driven). Immune system re-education (Phase 4) is best performed by dendritic cell or other vaccines, but most of these are investigational at this time.

Herb-Cancer Drug Interactions

There is a significant body of experimental and clinical data supporting a potentially positive role for botanicals in combination with conventional treatments in oncology. Using botanical medicines to counter the adverse effects of the toxic treatments used in conventional oncology would perhaps have surprised the Physiomedicalists, but is an intrinsic component of integrative approaches. Many chemopreventive compounds are associated with beneficial chemosensitization and radiosensitization, other plant compounds such as flavonoids disable the pumps that cause multidrug resistance. The immunomodulating and adaptogenic herbs described above protect against myelosuppression, which is the dose-limiting toxicity of many chemotherapeutic drugs, as well as increasing the ability of cancer patients to withstand the general stress of both chemo and radiation. Other herbs offer protection against specific toxicities of chemotherapy. Almost invariably these plant medicines are “pharmacological multitaskers”. Ginkgo for example protects against platinum induced renal toxicity, ototoxicity and neuropathy, and also acts as a radiation sensitizer by increasing local perfusion rates.13-16.}Green tea compounds not only enhance doxorubicin transport into malignant cells, it protects the myocardium against the cardiotoxic effects of the drug.17-21 From the integrative perspective, the list of potential beneficial interactions between botanicals and conventional cancer treatments is long and impressive.

This is not to say that “adverse” interactions between herbs and drugs are not theoretically possible, but the problem is often vastly overstated, for a particularly egregious example see the review by Sparreboom.22 Experimental results showing black cohosh synergizes with doxorubicin and docetaxel, and had no effect on Cytoxan or radiation but did decrease the effects of cisplatinum were extensively reported in the press as “herb interferes with chemotherapy”.23 Accurate clinical knowledge must inform appropriate proper care and management, this will both limit any potential adverse reactions and permit the therapeutic exploitation of beneficial interactions. The food model is once again relevant, particularly since a wide range of dietary ingredients (including grapes, grapefruit and other citrus, broccoli and other vegetables, spices, wine, tobacco, char grilled meat and many more) can alter human drug metabolizing (detoxifying) enzymes. In addition, individual differences in genetic, biochemical, biological and lifestyle demographics contribute enormous variability to drug disposition. Herbal medicine views each individual as a unique entity, following this patient-centered paradigm.

To date, there is not a single case report in the literature of any harmful interaction between a botanical and conventional antineoplastic treatment. For practitioners of botanical medicine, negative and uninformed secondary articles issuing dire warnings about adverse interactions between herbs and chemotherapy are sadly predictable.22 For cancer patients, their effect is to create fear, and to inhibit patients from seeking to use effective integrative strategies to enhance therapeutic outcomes.

Many questions asked by cancer patients (and care providers) cannot be answered definitively by the available scientific data, which potentially renders some decisions challenging. Sometimes enough research has not been done and sometimes the wrong question is asked by research, so the answer is unavailable. Often the mainstream response is to fall back on a fear based negative response because the “safety” a herb or dietary ingredient has not been positively established           and therefore may be “dangerous” Take the issue of soy. Pharmaceutical companies have engineered “Roundup™ ready” varieties of GMO soy crops, which are industrially processed into convenience, packaged food, like TVP, frozen soy burgers and sweetened soy milk. Often, unnaturally high amounts of isoflavones (which may be extracted from other legumes) are added. The epidemiological data about soy and chemoprevention has little to do with these products. When in doubt, herbalists recommend the traditional forms of soy, fermented, organic foods like miso and tempeh, taken in moderation, like any healthy dietary ingredient. This is another expression of the principle that the body acts upon food and medicine, obtaining the materials that it requires for restorative purposes. The wisdom of the body is a metaphor for the vital force, a term disdained by modern medicine. Interestingly, Walter Cannon, regarded along with Claude Bernard as the father of modern physiology, entitled his most important book in 1922, The Wisdom of the Body.

Our bodies have co-evolved with plants, both as food and medicine, for millions of years, and there is a deep connection between humans and plants at many levels, from the sacred to the subcellular. The question of how helpful or otherwise soy may be in different scenarios currently has no conclusive scientific answer, and there is no one-size-fits-all solution. In situations like this, where data is unavailable but patients have pressing questions, it is useful to remember the foundation of the food-medicine-poison model. The wisdom of the body (vital force) defines what is food, what is medicine, and what is poison. Concentrated isoflavone supplements may also have a role, but in endocrine dependent reproductive malignancies the use of high doses of these materials, unlike food, requires experienced management.24

CONCLUSION

Integrative strategies for treatment of cancer must include the benefits of botanical medicines. The difference between the vitalist core principles of herbal medicine and the mainstream medical model are profound, yet can be rendered accessible with a food-medicine-poison model of the therapeutic agents. This model is at the theoretical core of modern herbal medicine, and was brilliantly articulated by the Physiomedicalists at the turn of the 19th Century, particularly by Thurston and Lyle. The emerging molecular science of dietary chemopreventive compounds indicate the durability of this conceptual model as a therapeutic approach which will become increasingly important in the management of cancer, not only for prevention, but in the integrative treatment of advanced disease. Molecular vitalism is a key concept for advancing herbal medicine in the twenty first century.

References

1. Lyle T. Physio-Medical Therapeutics, Materia Medica and Pharmacy: Reprinted by NAMH, London, 1932; 1897.
2. Thurston J. The Philosophy of Physiomedicalism. Richmond, IA: Nicholson Printing and Manufacturing; 1900.
3. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta- analysis of prospective studies [see comments]. Jama 1998;279:1200-1205.
4. Sporn MB. Approaches to prevention of epithelial cancer during the preneoplastic period. Cancer Res 1976;36:2699-2702.
5. Bagchi D, Preuss H. Phytopharmaceuticals in Cancer Chemoprevention. Boca Raton: CRC Press; 2005.
6. Dorai T, Aggarwal BB. Role of chemopreventive agents in cancer therapy. Cancer Lett 2004;215:129-140.
7. Conney AH. Enzyme induction and dietary chemicals as approaches to cancer chemoprevention: the Seventh DeWitt S. Goodman Lecture. Cancer Res 2003;63:7005-7031.
8. Aggarwal BB, Takada Y, Oommen OV. From chemoprevention to chemotherapy: common targets and common goals. Expert Opin Investig Drugs 2004;13:1327-1338.
9. Chen C, Kong AN. Dietary cancer-chemopreventive compounds: from signaling and gene expression to pharmacological effects. Trends Pharmacol Sci 2005;26:318-326.
10. Milner JA. Molecular targets for bioactive food components. J Nutr 2004;134:2492S-2498S.
11. Bode AM, Dong Z. Targeting signal transduction pathways by chemopreventive agents. Mutat Res 2004;555:33-51.
12. Sengupta S, Toh SA, Sellers LA et al. Modulating angiogenesis: the yin and the yang in ginseng. Circulation 2004;110:1219-1225.
13. DeFeudis FV, Papadopoulos V, Drieu K. Ginkgo biloba extracts and cancer: a research area in its infancy. Fundam Clin Pharmacol 2003;17:405-417.
14. Ha SW, Yi CJ, Cho CK et al. Enhancement of radiation effect by Ginkgo biloba extract in C3H mouse fibrosarcoma. Radiother Oncol 1996;41:163-167.
15. Ozturk G, Anlar O, Erdogan E et al. The effect of Ginkgo extract EGb761 in cisplatin-induced peripheral neuropathy in mice. Toxicol Appl Pharmacol 2004;196:169-175.
16. Fukaya H, Kanno H. [Experimental studies of the protective effect of ginkgo biloba extract (GBE) on cisplatin-induced toxicity in rats]. Nippon Jibiinkoka Gakkai Kaiho 1999;102:907-917.
17. Sugiyama T, Sadzuka Y. Theanine, a specific glutamate derivative in green tea, reduces the adverse reactions of doxorubicin by changing the glutathione level. Cancer Lett 2004;212:177-184.
18. Hrelia S, Bordoni A, Angeloni C et al. Green tea extracts can counteract the modification of fatty acid composition induced by doxorubicin in cultured cardiomyocytes. Prostaglandins Leukot Essent Fatty Acids 2002;66:519-524.
19. Sugiyama T, Sadzuka Y. Enhancing effects of green tea components on the antitumor activity of adriamycin against M5076 ovarian sarcoma. Cancer Lett 1998;133:19-26.
20. Sadzuka Y, Yamashita Y, Kishimoto S et al. [Glutamate transporter mediated increase of antitumor activity by theanine, an amino acid in green tea]. Yakugaku Zasshi 2002;122:995-999.
21. Sugiyama T, Sadzuka Y, Tanaka K, Sonobe T. Inhibition of glutamate transporter by theanine enhances the therapeutic efficacy of doxorubicin. Toxicol Lett 2001;121:89-96.
22. Sparreboom A, Cox MC, Acharya MR, Figg WD. Herbal remedies in the United States: potential adverse interactions with anticancer agents. J Clin Oncol 2004;22:2489-2503.
23. Rockwell S, Liu Y, Higgins SA. Alteration of the effects of cancer therapy agents on breast cancer cells by the herbal medicine black cohosh. Breast Cancer Res Treat 2005;90:233-239.
24. Block KI, Constantinou A, Hilakivi-Clarke L et al. Point-counterpoint: soy intake for breast cancer patients. Integr Cancer Ther 2002;1:90-100.

i Of these, probably only Herceptin is the only drug that has proven itself of significant benefit, yet it is expoesnove enough that Her/2 neu positive breast cancer patients in England are not routinely given the drug due to its cost.

© October 2005, Jonathan Treasure

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