Integrative Medicine: Not Just Garnish
Integrative Medicine: Not Just Garnish
The term “integrative medicine” is fast replacing that of complementary and alternative medicine, or “CAM.” Integrative medicine (IM) is defined by its goal of integrating evidence-based interventions from complementary therapy and whole medical systems into conventional care. Various complementary therapies such as herbal/botanical medicine, meditation, yoga, acupuncture, and tai chi have been around for centuries in Europe, Asia, and the Middle East, and have been growing in popularity in the US for about three decades.
How Successful Have We Been With Achieving Integration?
One way to measure the pulse of integration is to look at the number of IM clinics, their locations and affiliations, and the breadth of what those clinics have to offer to patients. A Google search of “integrative medicine clinics” yields more than 8,700,000 hits. IM clinics are offered by a majority of the comprehensive cancer centers (although not all) and, not surprisingly, by many of the academic medical centers. What may be less well recognized is the extent to which integrative clinics are present in community centers throughout the US, particularly in states/regions where there are no National Cancer Institute (NCI)-designated or comprehensive cancer centers. Examples of this are the clinics in Great Falls, Montana; in Oklahoma City, Oklahoma; and in Midway, Kentucky.
A majority of the offerings from these clinics fall into the categories of mind-body or manipulative and body-based therapies; there are fewer offerings related to biologically based therapies (herbal/botanical medicine), now termed “natural products,” or whole medical systems, such as naturopathy, Ayurveda, or traditional Chinese medicine. This might be expected based upon the lack of available evidence and the potential risks related to drug/food interactions and toxicities associated with biologic therapies, whether they be standard pharmaceuticals, botanicals, or other “natural” products. There is an increasing knowledge about cytochrome P450 mechanisms and the ability of various pharmacologic agents to have an impact on the serum concentrations of each other, or to be affected by food, causing decreases in efficacy or increases in toxicities.[1-3]
Barriers to Integration
Barriers to the integration of natural products continue to consist of a limited evidence base, lack of standardized products, and little information on dose effects and drug/food interactions. The dearth of evidence in these areas is an important weakness since large surveys confirm herbs/dietary supplements remain one of the top modalities of CAM used by various segments of the population, with people enduring chronic illnesses or symptoms, such as cancer or pain, being among the most predominant users of such therapies.[4–6]
One example of the imbalance between use and evidence is menopausal symptoms, specifically, hot flashes. In one descriptive study, investigators performed a telephone survey about menopausal symptoms that included 110 breast cancer survivors and 73 women without breast cancer. Breast cancer survivors were more likely to experience menopausal symptoms and were seven times more likely to use alternative therapies to manage their symptoms. Despite their popularity, however, to date, randomized, controlled trials evaluating black cohosh, soy,[9,10] flaxseed, and vitamin E have not supported the benefits of these supplements with respect to hot flashes.
To safely and appropriately integrate natural products into conventional medicine, the evidence base must grow. Research scientists need to focus on identifying the properties of various active ingredients, and on how various aspects of plants or other biologically active substances may be additive or synergistic. They also need to provide insight on how best to standardize the products, while exploring the dose response, drug/food interactions, and toxicities. For the present, the population of people who use biologically based therapies needs to be educated about their potential risks, the limitations of the knowledge to date, and the need to seek professional expertise about potential benefits and proper use.
Non-Biologically Based Therapies: More Readily Integrated, but Understudied
Modalities that are not biologically based (such as mind-body, manipulative, and energy-based therapies) have been more readily integrated into cancer care. However, they continue to be understudied or are often studied using unfocused and multiple endpoints, and inadequate control groups. Therefore, clinically, these interventions seem to be included in the offerings of integrative centers as adjunctive therapies when resources are available, based on a philosophy of “garnish”—an added service that is not imperative but nice to offer because patients like them and they appear to present little risk. It is not clear that there is an acknowledgement of how critically important, or integral, it is to address the patient’s psychosocial and physical environment (including diet, activity, and stress) to achieve optimal health.
The critical nature of incorporating the care of the mind and spirit into the care of the body is a philosophy that is embedded in many of the non-Western cultures. In the US, to fully appreciate this multidimensional focus on health will require a culture change, one that will need to be preceded by rigorous evidence. One of the elements of evidence that would help to move this culture change forward relates to physiologic effects and specific or additive effect-size contributions of the mind and spirit to patient outcomes, particularly those related to symptom management. There are some investigators who are beginning to demonstrate those types of outcomes.
For example, Ornish, Kottler, Dod, and others have published some of the few studies to show beneficial changes in teleomere (DNA at the end of a chromosome) length, endothelial blood flow, and lipid measures resulting from lifestyle (activity, diet, and stress reduction) interventions. Reductions in lipids with lifestyle interventions, for example, have been found to be similar to what can be accomplished with approved pharmaceuticals (ie, lipid level reductions of 25% to 30%). In the realm of symptom management, numerous meta-analyses and head-to-head comparison trials have demonstrated equal efficacy with respect to sleep disturbances for cognitive behavioral therapy and pharmacologic sleep therapy.[17–19] A trial evaluating yoga for cancer-related fatigue has shown an impact on cortisol slope and heart rate variability. Brain imaging studies in acupuncture have demonstrated activation of different mechanisms in the central nervous system with sham acupuncture versus true acupuncture, and similar studies in hypnosis demonstrate differential brain activity with various aspects of the hypnosis process, vs normal rest states or states observed in patients treated with guided imagery.[22–27]
The mind-body connection is perhaps illustrated most dramatically by a study published evaluating dopamine release by PET (positron emission tomography) scan in patients with known Parkinson Disease (PD). Patients on levodopa with mild to moderate PD were taken off of their anti-PD medication 12 to 18 hours before a baseline PET scan. They were then given open-label levodopa/carbidopa and scanned an hour later. On the second day, they were randomized to one of four groups and told they had a 25%, 50%, 75%, or 100% chance of getting levodopa or a placebo. They were then given their assigned drug and scanned an hour later, with exactly the same procedure and timing used to collect the day 1 scans. The scans on day 2 revealed that the group of patients who were told they had a 75% chance of getting levodopa had more dopamine release than the other groups.
What the patients did not know, however, was that on day 2, all patients in every group had received a placebo. (There was a very ethically sensitive consent form involved and the institutional review board vetted the implementation of this study.) Therefore, the results indicate that the dopamine release seen in the PET scans was in response to an expectation of receiving an active drug, when in fact all patients received a placebo. The investigators explain in the discussion section of their paper that it makes sense that the response was best seen in the 75% group, as dopaminergic activation is optimal when rewards are likely but not absolutely certain (as in the 100% group). Moreover, however, the striking insight gained from this study is that dopamine release was triggered by verbal instruction and expectations. The potential of the mind to influence health and wellness is very much underappreciated.
Another major weakness of the research into mind-body and manipulative/body-based therapies is a lack of appropriate control groups to account for nonspecific effects of social interaction and natural changes over time. Studies to delineate the critical elements of complex, time-intensive interventions as well as attention to dissemination of the proven therapies are sorely needed. The study on dopamine release is, again, an important lesson in the need to design studies that accurately attribute outcomes to the intervention. Appropriate control groups are a critical element in this endeavor.
We still have much to do to fully understand the potential of complementary therapies as important elements in cancer treatment and health. Mind-body and body-based interventions may be able to improve health and prevent disease as effectively as pharmacologic agents—without the toxicities associated with pharmacologics, and as adjuncts to pharmacologic therapies they may help to maximize health and diminish disease with less toxicity. Comprehending the powerful contribution to health and illness of a person’s behaviors, psychosocial concerns, and physical environment, and delineating what positive effects complementary therapies contribute to these elements, are critical goals that can help to shape the direction of healthcare reform. In times of great flux and uncertainty, as in healthcare and our economy, there is opportunity to achieve real change. Let us seize the chance to deepen our knowledge about truly integrated medicine, so that our patients can fully realize its significant benefits.
Meet Our Guest Editor, Georgia Decker
Georgia M. Decker, APRN, ANP-BC, CN, AOCN, earned her BSN from Carlow University Pittsburgh, Pennsylvania, a Masters in Nursing with a clinical specialty in oncology from Russell Sage College, Troy, New York and her post-Masters certificate as an Adult Nurse Practitioner from Syracuse University, Syracuse New York. Ms. Decker is certified as an Advanced Oncology Certified Nurse (AOCN®) and has earned certification in Clinical Nutrition (CN®). Georgia's interest in complementary and alternative medicine (CAM) therapies was sparked through with conversations with patients. Ms. Decker is the editor of An Introduction to Complementary Therapies and coauthor of the Handbook of Integrative Oncology Nursing: Evidence-Based Practice, and she was the first column editor for the Integrated Care column in the Oncology Nursing Society publication, Clinical Journal of Oncology Nursing (CJON).
Financial Disclosure: The author and Guest Editor have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
1. Foster BC, Vandenhoek S, Hana J, et al: In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 10(4):334–342, 2003.
2. Komoroski BJ, Parise RA, Egorin MJ, et al: Effect of the St. John’s wort constituent hyperforin on docetaxel metabolism by human hepatocyte cultures. Clin Cancer Res 11(19 Pt 1):6972–6979, 2005.
3. Zhou S, Gao Y, Jiang W, et al: Interactions of herbs with cytochrome P450. Drug Metab Rev 35(1):35–98, 2003.
4. Barnes PM, Bloom B, Nahin RL: Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Report 12:1–23, 2008.
5. Bernstein BJ, Grasso T: Prevalence of complementary and alternative medicine use in cancer patients. Oncology (Williston Park) 15(10):1267–1272; discussion 1272–1278, 2001.
6. Navo MA, Phan J, Vaughan C, et al: An assessment of the utilization of complementary and alternative medication in women with gynecologic or breast malignancies. J Clin Oncol 22(4):671–677, 2004.
7. Harris PF, Remington PL, Trentham-Dietz A, et al: Prevalence and treatment of menopausal symptoms among breast cancer survivors. J Pain Symptom Manage 23(6):501–509, 2002.
8. Pockaji B, Gallagher J, Loprinzi C, et al: Phase III double-blinded, randomized trial to evaluate the use of black cohosh in the treatment of hot flashes: A North Central Cancer Treatment Group Study. J Clin Oncol 24(18):2836–2841, 2006.
9. North American Menopause Society: Treatment of menopause-associated vasomotor symptoms: Position statement of The North American Menopause Society. Menopause 11(1):11–33, 2004.
10. Quella SK, Loprinzi CL, Barton DL, et al: Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial [see comment]. J Clin Oncol 18(5):1068–1074, 2000.
11. Pruthi S, Qin R, Terstreip SA, et al: A phase III, randomized, placebo-controlled, double-blind trial of flaxseed for the treatment of hot flashes: North Central Cancer Treatment Group N08C7. Menopause 19(1):48–53, 2012.
12. Barton DL, Loprinzi CL, Quella SK, et al: Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. J Clin Oncol 16(2):495–500, 1998.
13. Ornish D, Lin J, Daubenmier J, et al: Increased telomerase activity and comprehensive lifestyle changes: a pilot study. Lancet Oncol 9(11):1048–1057, 2008.
14. Dod HS, Bhardwaj R, Sajja V, et al: Effect of intensive lifestyle changes on endothelial function and on inflammatory markers of atherosclerosis. Am J Cardiol 105(3):362–367, 2010.
15. Ferdowsian HR, Barnard ND: Effects of plant-based diets on plasma lipids. Am J Cardiol 104(7):947–956, 2009.
16. Ornish D: Mostly plants. Am J Cardiol 104(7):957–958, 2009.
17. Epstein DR, Dirksen SR: Randomized trial of a cognitive-behavioral intervention for insomnia in breast cancer survivors. Oncol Nurs Forum 34(5):E51–E59, 2007.
18. Morin CM, Culbert JP, Schwartz SM: Nonpharmacological interventions for insomnia: A meta-analysis of treatment efficacy. Am J Psychiatry 151(8):1172–1180, 1994.
19. Morin CM, Hauri PJ, Espie CA, et al: Nonpharmacologic treatment of chronic insomnia. An American Academy of Sleep Medicine review. Sleep 22(8):1134–1156, 1999.
20. Cohen L, Chandwani N, Raghuram N, et al: Effect of yoga on QOL, cortisol rhythm and HRV for women with breast cancer undergoing radiotherapy. J Clin Oncol 29(suppl): abstr 9009, 2011.
21. Harris RE, Zubieta JK, Scott DJ, et al: Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on mu-opioid receptors (MORs). Neuroimage 47(3):1077–1085, 2009.
22. Faymonville ME, Laureys S, Degueldre C, et al: Neural mechanisms of antinociceptive effects of hypnosis. Anesthesiology 92(5):1257–1267, 2000.
23. Faymonville ME, Roediger L, Del Fiore G, et al: Increased cerebral functional connectivity underlying the antinociceptive effects of hypnosis. Brain Res Cogn Brain Res 17(2):255–262, 2003.
24. Hofbauer RK, Rainville P, Duncan GH, et al: Cortical representation of the sensory dimension of pain. J Neurophysiol 86(1):402–411, 2001.
25. Maquet P, Faymonville ME, Degueldre C, et al: Functional neuroanatomy of hypnotic state. Biol Psychiatry 45(3):327–333, 1999.
26. Milling LS, Kirsch I, Allen GJ, et al: The effects of hypnotic and nonhypnotic imaginative suggestion on pain. Ann Behav Med 29(2):116–127, 2005.
27. Schulz-Stubner S, Krings T, Meister IG, et al: Clinical hypnosis modulates functional magnetic resonance imaging signal intensities and pain perception in a thermal stimulation paradigm. Reg Anesth Pain Med 29(6):549–556, 2004.
28. Lidstone SC, Schulzer M, Dinelle K, et al: Effects of expectation on placebo-induced dopamine release in Parkinson disease. Arch Gen Psychiatry 67(8):857–865, 2010.