Understanding Acupuncture Research

Paul Reller, L.Ac.

Acupuncture and its physiological effects and specific benefits has perhaps been the most studied manual medical therapy in world history. Not only does acupuncture have a rich history of thousands of years of data accumulation on clinical effectiveness, modern science has sought to understand and measure the effects of acupuncture objectively, not only with outcome measures, but also with the metabolic and physiological effects evident from acupuncture stimulation.

When analyzing the evidence of needle trigger point stimulation, as well as electrical stimulation, and other more high tech types of stimulation, notably cold laser, at the trigger points, what is perhaps most important are the physiological effects, rather than the specific outcomes. The reason for this is that trigger point stimulation with metal needles is not strictly a type of allopathic approach to medicine, but rather a modulating effect that is holistic and systemic. For this reason, analysis of the effects of acupuncture requires a little more thought than the analysis of the allopathic effects of specific chemicals on specific cellular mechanisms. Research in recent years has found that electroacupuncture stimulation affects pain modulation and promotes tissue healing by stimulating hypothalamic function and prompting a metabolic cascade, and in the past, endorphin and other enkaphlins were found to be increased in central and peripheral nervous system pain pathways in response to acupuncture stimulation. As research continues, we find the effects of acupuncture to be broad.

What do I mean by allopathic approach? Of course, this term has been used in a number of contexts throughout the years, and this can lead to controversy. In modern terms, allopathic approach would signify the use of therapy that is not biodientical or stimulating of normal physiological responses to cure a disease. Use of pharmaceutical chemicals that are not identical to the body's own chemistry to effect specific changes, and use of surgical or other devices to alter the anatomy or physiology rather than restore it may be used as examples of allopathic approach. The use of benign needle stimulation at trigger points, and the use of bioidentical chemicals from plants, animals or even minerals, to stimulate normalization of homeostatic mechanisms is not allopathic. Research findings must take this difference into consideration when analyzing the significance of positive findings, as well as in the design of acupuncture studies.

The point is, that acupuncture effects are modulating, and different techniques of stimulation, or even reaction to the needles by the individual patient, may produce opposite effects physiologically, and thus, the anaylysis of acupuncture must incorporate these variables in order to make a thorough and competent evaluation of the effects of acupuncture. The present scientific method controls for variables by reducing these variables and extraneous effects on outcome, but this is inadequate to fully produce an unbiased result with acupuncture. Typing of the patient and consistency with physiological effects should be controlled. The problems with setting up the scientific study to effectively measure results is difficult, but studies that measured both objective physiological effects as well as outcomes would be an improvement.

In analyzing the outcomes of past and present study of acupuncture it may be helpful to actually take a look at the details of the study and use your own knowledge of the problems with double-blinded studies of acupuncture, as well as the knowledge of physiological effects and the modulating holistic effects expected to adequately form an opinion, especially when the outcome measures are significantly positive.

Understanding the physiological effects of acupuncture

One way to better understand the actual potential benefits from acupuncture is to incorporate measures of physiological effects into the study of a particular type of needle stimulation on a particular type of patient group. For this reason, the subject of actual physiological effects of needle stimulation is the subject of much scientific interest.

The study of actual physiological effects has also elucidated the subject of placebo effect in acupuncture. Since there has been a high degree of difficulty in setting up a placebo effect that is blinded to both the patient and the physician performing the treatment, studies have relied on so-called sham acupuncture stimulation that is either actual stimulation with acupuncture needles at alternate points, or use of alternate methods of stimulation at the same points. The alternative method is to use a type of device that seems like a needle stimulation to the blinded patient, but not to the physician, resulting in a single-blinded study. All of these studies have generally shown remarkable beneficial outcomes for both the actual needle selection and the so-called sham, or alternate selection or sham device stimulation at the same points. The difference in outcome measures between the studies of acupuncture stimulation and these so-called sham techniques has been used to determine proof of beneficial effect greater than placebo. Any rational scientist can see the problem with this type of outcome measurement, since the potential for beneficial effects from the so-called sham methods is great. In England, a study was set up in 2007 to measure physiological differences between real needle stimulation and placebo stimulation. The patients were blinded to the difference, but the outcome measures were dramatically different in terms of physiological effects. This study, at the University College of London and Southhamptom College, proved with PET scan study that a placebo stimulation mimicking acupuncture, excited areas of the brain associated with touch, while the real acupuncture stimulation with needles excited areas of the brain associated with endorphin and dynorphin release and pain modulation (insular). This was proof that the effects of real acupuncture needle stimulation had a physiological effect different from placebo, even though the placebo stimulation had potential for positive CNS response.

In 2007, a unique study of acupuncture effects was conducted at the Martinos Center for Biomedical Imaging, Massachusetts General Hospital (Pain 130 (2007) 254-6). Here, functional MRI was used to evaluate real (verum) and sham acupuncture stimulation at a single point (LI4) on chronic carpal tunnel patients and health controls. The researchers found that chronic pain patients responded differently in the brain from healthy controls, and that real acupuncture stimulation in these patients exerted a beneficial modulating activity in the hypothalamus balance with amygdala activity, whereas such response did not occur in healthy controls. This response was measured immediately and in follow-up, demonstrating the long-lasting effects of this beneficial hypothalamus and amygdala stimulation. The modulation of these pain centers produced not only a change in sensed pain, but measurable functional changes in the inter-digit separation distance of the hand affected. Since this seminal study, the researchers, working with Harvard Medical University, have proven that there is a measurable difference in response to superficial point stimulation and real acupuncture stimulation. The real acupuncture affects the brain stem and centers, while the superficial, or sham, acupuncture stimulated the cortex, affecting only a temporary sensation of pain relief. Placebo effects were thoroughly studied as well, by Professor Ted Kaptchuk, who proved in a randomized single-blinded controlled trial of IBS patients receiving placebo acupuncture, in 2008, that the placebo effect of a caring confident physician-patient relationship, typically delivered in a clinical setting with acupuncture, produced a significant outcome benefit over placebo acupuncture alone, or the outcome on a patient waiting list with no treatment. Such research has expanded the objective assessment of the acupuncture treatment outcome. The use of double-blinded “placebo” controlled clinical trials, where the patients received only limited superficial acupuncture, without an actual treatment utilizing the physician-patient relationship, were designed to find failure of the acupuncture over placebo and deny care. We see now that this study design did not adequately assess the real acupuncture treatment outcomes. The remarkable outcome, though, is that even with this biased study design, acupuncture proved itself in human clinical trials.

To elucidate, let us take a recent study set up to measure the outcome of acupuncture stimulation at a single point to reduce post-operative nausea and vomiting. A 2004 study at the University of Heidelberg, Germany, measured the outcomes of acupuncture stimulation at the point P6 on the wrist with so-called placebo acupuncture stimulation at the same point. Nausea in post-operative patients with gynaecological surgery, within 24 hours after surgery, was measured by the need for antiemetic medication as well as the secondary outcome of reduced incidence of vomiting. The acupuncture group showed a reduction to 48.9% of the usual need for medication, while the so-called placebo stimulation of the point showed a reduction to 67.6% from normal need for medication. The incidence of vomiting, a secondary measurement, was reduced from normal statistics of 39.6% of paitents, to just 24.8%. The study included two subgroups that received the acupuncture stimulation before surgery, with one group receiving the stimulation before anesthesia, and the other after the start of anesthesia. The study outcome reported no significant effect over placebo for the acupuncture stimulation. This article was published in Anaesthesia Vol. 59;(2);142-149; 2004 Blackwell Publishing Ltd; Wiley Interscience. With such a significant reduction in need for antiemetic medication and vomiting, and considering the limitations of the strength of stimulation and lack of individual adjustment by a physician post-operatively, the summation of findings seems rather harsh. When looking at the so-called placebo and realizing that it too was a significant form of acupuncture trigger point stimulation, comparison to placebo with about a 20% greater effect for the real acupuncture, and P = 0.07, and a reduction in incidence of vomiting by about 15%, P = 0.03, seems to be a rather impressive outcome. The study authors suggested that this study showed no significant benefit over placebo. When comparing this to pharmaceutical research, where the placebo is a pill with zero positive effect expected, and considering that one may look in any pharmacological clinical physician's guide and see many standard medications outperforming placebo by less than 6%, the outcome judgement seems unrealistic. This shows that the current state of research does not value realistic understanding of the parameters of acupuncture research compared to pharmaceutical research when publishing research summaries.

The British Medical Association went so far as to state that even the placebo effects of acupuncture should not be discounted, and stated: "The placebo effect in itself should not be a reason for discounting complementary therapy research, as the usefulness of a medical intervention in practice is different from asesssing formal efficacy." In fact, many expensive pharmaceuticals in clinical study barely outperform the placebo pills, and meta-analysis has revealed that the placebo effects overall in clinical studies has nearly doubled since 1960. While the implications of this fact are complex, it nevertheless implies that evaluation of acupuncture compared to placebo is not as simple and straightforward at some would have us believe.

When looking at the above study, one should realize that in actual medical practice, the physician performing the acupuncture could increase the positive benefit of the treatment considerably by adding other acupuncture points, by individualizing the treatment, and by responding to the individual patient during the treatment time. Experience and ability of the individual acupuncturist would also play a part in improving the outcome clinically. When this is compared to pharmaceutical outcomes, there is no chance that the outcome could be improved from the study parameters when using medication, if the study is using the optimal dosage and type of drug. Positive outcomes in acupuncture research should be viewed with greater respect rather than less respect, and this is not currently the case.

The study of physiological effects of acupuncture reached a new plateau in 1998 with the fMRI studies of neurological effects from distal acupuncture point stimulation at the University of California Irvine, Susan Samueli Center for Integrative Medicine. Here, Michael E. Phelps, creator of the PET scanner and UCLA pharmacology chair and Norton Simon Professor, (NOTE: Edward J. Hoffman (deceased July 9, 2004), UCLA professor and co-inventor of the PET scan with Dr. Gordon L Brownell (deceased Nov. 23, 2008, are distinguished from the creator of the device), sponsored a collaboration study between the UC Irvine Departments of Radiology, Psychiatry, Human Behavior and Opthamology, and three prestigious South Korean Colleges, including the College of Medicine at Kyung Hee University, Seoul, Korea. This study was in response to positive benefits of treatment that Professor Phelps observed on himself when treated in South Korea with acupuncture. Prior to this experience, Professor Phelps did not believe in the scientific efficacy of acupuncture. This study used points associated with the treatment of ocular diseases on the side of the foot, Taiyang channel, and measured effects of stimulation on the corresponding brain cortices using functional MRI to map brain activity. The points used are typically called UB67, UB66, UB65, and UB60. The Korean researchers divided the study participants into Yin type and Yang type to explain differences in measurable outcomes with the same type of stimulation. The controls used were visual light stimulation previously used in fMRI studies of the occipital visual cortex, and an atypical acupuncture point stimulation on the same foot, but away from the meridian. The conclusions reached were that acupuncture stimulation could work by stimulating a corresponding brain cortex area via the CNS, and thereby stimulating a homeostatic chemical or hormonal release via the CNS to a diseased or disordered tissue. The stimulation by the acupuncture needling was very similar to stimulation with methods of visual stimulation previously studied. The study was published in Proc. Natl. Academy of Science, USA; Vol. 95, pp. 2670-2673, March 1998, Physiology. Much criticism of this study was engendered by standard medicine, and a partial retraction of findings was published due to this criticism on June 21, 2006, but the bulk of the research findings remained, and the researchers at UC Irvine went on to conduct a number of well designed studies to examine the cardiovascular metabolic cascade stimulated by acupuncture.

Smaller pilot studies of the physiological effects of acupuncture, such as the 2004 Portland State University collaboration with Kaiser-Permanente Center for Health Research, D. Tsunami, A. Colbert et al, study of electrocardiogram and electrodermal responses to needle stimulation, were conducted, and also showed significant physiological effects. In this study, significant effects were also noted at the so-called control point, but the authors conceded that the point selected was close enough to the point studied, called ST36, that stimulation may have also elicited the normal point response. In TCM literature, past Chinese physicians have noted that stimulation of a point in the approximate area of the exact point location will have a beneficial effect, albeit smaller. There is also significant debate in TCM history as to the exact location of the points in many instances. It does seem historically, that the response to the needle stimulation is more determinant of point location than a standard skin charting and measurement. Frequently, study design does not take this into consideration, or perhaps uses this fact to bias the study outcome against acupuncture by choosing a placebo point that is also active. This study cites 15 other small studies of positive physiological effects conducted between 1993 and 2003. The researchers conclude that the significant physiological effects measured on heart response from stimulation of points below the knee could be attributed to psychological responses of the patient, or placebo effect. Once again, do we consider that measurable physiological effects are being discounted because of apriori assumptions and bias by the researchers?

There are examples of quality acupuncture study by researchers that are not biased against the profession, and that choose placebo points that are not as likely to produce similar reactions to that of the chosen study points. An example would be a study entitled: The management of cancer-related fatique after chemotherapy with acupuncture and acupressure: A randomised controlled trial, published in Complementary Therapies in Medicine, Vol. 15;(4):228-237, conducted at the University of Manchester, School of Nursing, Manchester, UK; Nov 13, 2006. Forty-seven patients with post-chemotherapy moderate to severe fatique were randomised to an acupuncture group receiving 6 20-minute treatments over 2 weeks, a second group that was taught to massage the points and did so daily, and a third group that was taught to massage points not considered effective. The measured outcomes showed a 36% improvement in the acupuncture group, a 19% improvement in the acupressure group, and a 0.6% improvement in the sham acupressure group. Here we see that even manual stimulation near the acupuncture point produced good results, but not as good as needle stimulation, but that the same manual stimulation at points not considered viable produced almost no results. Scientific observation should show you that acupuncture was shown to be effective, but that sham treatment at the points was also proven beneficial. This finding should help you to analyze the aforementioned ECG study at Portland, and see that the researchers used a needle stimulation very close to the actual point, resulting in positive results lower than the study point. This should be expected and should not discount the study.

Other examples of physiological effects in acupuncture study are now numerous, although accessibility of the studies performed in China, Japan and Korea is often problematic. An example of recent study of note in the West is a study aired on BBC TV Alternative Medicine showed that deep needle acupuncture therapy can actually deactivate the brain's limbic system, or pain sensitization, making this medical practice anesthaetic. Evidence was derived from fMRI study in this study also.

Towards a better understanding of outcome measures in clinical trials of acupuncture

The British Medical Association in 2007 stated that the adherence to trial standards set for pharmaceutical research is unfair to the study of acupuncture. It stated that: "trials of acupuncture must be single blind", and that randomized controlled trials of patients must provide evidence "only in an experimental setting on a selected group of patients", in order to decrease the unfair manipulation of acupuncture trial data. In trying to understand whether acupuncture is truly evidence-based, one must be able to distinguish biased study design from unbiased, and be able to consider the physiological benefits along with the symptom outcome measures. Often, the study itself needs to be examined to see if evidence of proven benefit exists even though the study authors state in summary that the results are inconclusive or that benefit is not proven over placebo.

Is there a systemic bias in our medical system that undermines our understanding of the evidence of benefit from acupuncture? To examine such bias, let's look at a recent meta-analysis conducted in China, where there is still much criticism by standard medicine of TCM. This University of Hong Kong study examined 12 research databases for clinical trials of acupuncture to treat insomnia. Randomised, controlled trials were chosen, with acupuncture compared to placebo, sham acupuncture, or no treatment, or acupunucture combined with another standard therapy compared to that standard therapy without acupuncture added. Studies that compared acupuncture to other treatment, without comparison to placebo, sham or no treatment in a blinded setting were excluded. Because of this, only 7 trials were included. The meta-analysis found that acupuncture and acupressure may help to improve sleep quality score compared to placebo (p = 0.006) or no treatment (p = 0.002). The study authors concluded that the small number of acceptable randomised controlled trials, together with poor methodological quality and significant clinical heterogeneity, means that current evidence is not sufficiently extensive or rigorous to support the use of any form of acupuncture for the treatment of insomnia. Because these trials deemed acceptable were not standardized, numbered only 7, and because the authors felt that variances in outcome measurements must imply poor methodological quality, the meta-analysis was negative to support acupuncture, even though the trials that met inclusion all proved significant benefit. The problems inherent in study design with double-blinded trials was not considered, and hence the available studies in 12 databases were limited to 7 trials. Inherent problems with standardized outcome measures in a field where study design problems are still not solved, and funding is poor, are not considered. The end result is that by standards of large clinical trials designed for pharmaceuticals, and paid for with megabucks of pharmaceutical companies, that acupuncture study does not compare well. This is the criteria with which such meta-analysis is prepared for Cochrane Database Systems Review. No mention of funding for this meta-analysis at the University of Hong Kong Pediatrics and Adolescent Medicine is mentioned.

Information Resources

The purpose of this article is not to present acupuncture research, but merely to point out the problems with the industry bias and manipulation of the positive research in acupuncture. A few links below help to illustrate how specific and detailed the scientific proofs are, as well as to illustrate how study design, understatement, and summary bias has created an atmosphere of negativity toward acupuncture research that is blatantly used to deny coverage and care, not to promote greater scientific understanding and successful utilization for the public good.

1. Harvard Medical School study on the CNS modulatory effects of acupuncture stimulation. http://www3.interscience.wiley.com/journal/70000102/abstract?CRETRY=1&RETRY=0
2. 1998 fMRI study of distal acupuncture stimulation and physiological effects in the brain at the University of California Irvine can be seen at http://www.pnas.org/content/95/5/2670.full.pdf?ck=nck
3. The study designed in Britain to eliminate study design bias can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/18054724
4. A 2007 study by the Martinos Center for Biomedical Imaging and the Massacusetts General Hospital in coordination with Harvard Medical University, proved that real acupuncture has modulating and long-term effects on the brain centers, the hypothalamus and amygdala, while sham acupucture, or superficial stimulation affected on the cortex sensation: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1997288/
5. A German journal article discussing problems with acupuncture trials is very illuminating from a number of perspectives: http://www.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=110416&Ausgabe=234157&ProduktNr=224242&filename=110416.pdf This article is titled Forschende Komplementarmedizin 2007;14:371-375 Journal Club - Acupuncture for Hypertension: A Tale of Two Trials, and you may need to scroll down the page to Further Sections 371 Journal Club and click on the Article PDF Free Access. If this link fails, you may try searching under this title.
6. An August 24, 2010 article in the New York Times Health section, finally presents a truthful outlook at how acupuncture research is designed by the medical industry to achieve outcome headlines that are negative. This article focuses on an industry study of knee pain which utilizes a supposedly sham acupuncture comparison that is so close to the so-called real acupuncture therapy in the study as to be laughable, with the study summary stating that the so-called real acupuncture was not proven to significantly outperform the so-called sham acupuncture, but failing again to report the positive medical effects of both treatments: http://well.blogs.nytimes.com/2010/08/23/studying-acupuncture-one-needle-prick-at-a-time/