Acupuncture: An Overview of Scientific EvidenceBY MEL HOPPER KOPPELMAN, DAc, MSc, MSc
Strength of evidence
EVIDENCE FOR ACUPUNCTURE IS GROWING EXPONENTIALLY
Research into acupuncture as a medical treatment has grown exponentially in the past 20 years, increasing at twice the rate of research into conventional biomedicine. Over this period, there have been over 13,000 studies conducted in 60 countries, including hundreds of meta-analyses summarizing the results of thousands of human and animal studies 1. A wide-variety of clinical areas have been studied, including pain, cancer, pregnancy, stroke, mood disorders, sleep disorders and inflammation, to name a few.
SUMMARISING ACUPUNCTURE'S EVIDENCE
With nearly 1,000 systematic reviews of acupuncture, getting a sense of what the evidence shows can be a challenge. Fortunately, the entire literature base was summarized in 2010 by the Australian Department of Veteran Affairs 2. This review was updated in 2014 by the US Department of Veteran Affairs and then again in 2017 by John McDonald and Stephen Janz, the authors of the Acupuncture Evidence Project 3.
The Acupuncture Evidence Project reviewed the effectiveness of acupuncture for 122 treatments over 14 clinical areas. They found some evidence of effect for 117 conditions. “Our study found evidence for the effectiveness of acupuncture for 117 conditions, with stronger evidence for acupuncture’s effectiveness for some conditions than others. Acupuncture is considered safe in the hands of a well-trained practitioner and has been found to be cost-effective for some conditions. The quality and quantity of research into acupuncture’s effectiveness is increasing.” Acupuncture Evidence Project, p55
MEDICAL GUIDELINE RECOMMENDATIONS FOR ACUPUNCTURE
While acupuncture enjoys high-level clinical evidence for dozens of conditions, translating trial research into official medical guidelines can take time. However, a recent review examined clinical guideline recommendations from around the world made by a variety of groups including government health institutions, national guidelines, and medical specialty groups. Over a 27 year period, they found 2189 positive recommendations for acupuncture for 204 health problems, mainly in guidelines published in North America, Europe and Australasia 4. These official recommendations indicate that acupuncture’s evidence is now acknowledged by medical experts and that acupuncture is no longer ‘alternative.’ Indeed, this new data illustrates that acupuncture is one of the most widely recommended treatments in modern medicine.
PUTTING ACUPUNCTURE IN CONTEXT: EVIDENCE FOR OTHER CONDITIONS
Acupuncture enjoys a high level of evidence for a variety of conditions. However, it can be challenging to understand the significance of this without comparison to the evidence for other commonly recommended treatments.
Looking at the evidence for currently recommended biomedical treatments, a recent review published in the proceedings of the Mayo Clinic in 2013 found that studies that examined the evidence for the standard of care (i.e. what doctors usually prescribe) recommended against current practice 46% of the time. In other words, from 2001-2010, for nearly half of the evaluated interventions, 146 in total, the recommendation to treat patients with these interventions was reversed 5. Another recent review also found that only about half of standard treatments were evidence-based: “An empirical evaluation of the Cochrane Database of Systematic Reviews found that the existing evidence base was unable to support or refute 49% of interventions, and 48% of American College of Cardiology recommendations were supported by expert opinion only”6. In short, nearly half of all medical practices do not have positive evidence for their use and are not considered to fall into the category of ‘evidence based medicine.’
Related to treatments that lack evidence, the overuse of medical interventions, defined as, “the provision of medical services that are more likely to cause harm than good,” is also a global problem. “A more recent systematic review of global overuse categorized 83 overused or low-value services from studies including large sample sizes (more than 800 patients). These authors identified studies from four countries (with US studies predominating) and found that rates of overuse of various services ranged from about 1 to 80 percent”7. These included treatments such as traction for patients with low back pain and testing such as tumour marking studies for patients with previous breast cancer.
With such high use of medical treatments that are more likely to harm than help, it becomes axiomatic that in many clinical situations, patients would be best served to start with safer treatments, such as acupuncture, when indicated.
While harms from appropriately administered treatments are prevalent, harms and deaths from medical error are rampant. According to a recent review published in the British Medical Journal, medical error is the 3rd most common cause of death in the U.S., with a quarter of a million deaths in 2013 alone 8.
ACUPUNCTURE HEAD TO HEAD
Using a review method known as a Network Meta-analysis, it is possible to evaluate various treatments for the same condition in a head to head analysis. Below are a few examples of how acupuncture compares to other treatments.
- A 2013 network meta-analysis comparing physical treatments for osteoarthritis of the knee found that, when looking at high quality studies, acupuncture had the largest effect compared to usual care out of the conditions evaluated, out-performing exercise, sham acupuncture, and weight-loss 9.
- A 2015 network meta-analysis comparing treatments in addition to exercise for shoulder impingement syndrome found that acupuncture was the most effective adjunctive treatment out of 17 interventions, outperforming all other adjuncts such as steroid injection, NSAIDs, and ultrasound therapy 10.
- A 2016 comparison of 20 treatments for sciatica ranked acupuncture as 2nd most effective after the use of biological agents, outperforming manipulation, epidurals, disc surgery, opioids, exercise, and an invasive procedure called radio-frequency denervation, which came in last 11.
- In 2018, a network-meta-analysis found that acupuncture was more effective than drugs for treating chronic constipation and with the fewest side-effects 12.
HOW DOES ACUPUNCTURE WORK? A LOOK AT SOME MECHANISMS
The mechanisms underlying how acupuncture relieves pain have been extensively researched for over 60 years. Sensory nerve pathways involving specialized nerve fibers (Aδ, Aβ and C, to be precise) and descending nervous system pathways have been mapped. Numerous biochemicals have been identified including opioid and non-opioid neuropeptides, and neurotransmitters such as serotonin, norepinephrine, dopamine, cytokines, glutamate, nitric oxide, and gamma-amino-butyric-acid (GABA). Acupuncture analgesia has been shown to involve several classes of naturally produced opioid neuropeptides including enkephalins, endorphins, dynorphins, endomorphins, and nociceptin (also known as Orphanin FQ). Among the non-opioid neuropeptides, substance P (SP), vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP), which plays a central role in the pathogenesis of migraine, have been investigated for their roles in both the analgesic and anti-inflammatory effects of acupuncture 13 14.
Many biochemical and signaling pathways have been identified as playing a direct role in how acupuncture achieves its clinical effects, but perhaps the most central pathway that acupuncture uses, one that helps explain how it is effective in such a diverse array of clinical areas, is that acupuncture has been demonstrated to directly initiate a process called purinergic signaling, a primitive 15 and ubiquitous system in the body using adenosine and ATP for signaling and regulation in all tissues and organ systems 16. It is now understood that all nerve transmission requires ATP as a co-factor and the that the body uses purine levels as a primary background signal of both healthy function and tissue damage. Studies on mice demonstrate that those that were bred to be unable to bind to adenosine did not have pain relief from acupuncture nor any of the chemical changes associated with acupuncture pain relief, while the normal mice did 17 18 and this effect was repeated in humans 19.
Purinergic signaling has been demonstrated to play a central role in such diverse clinical areas as migraines and headaches 20, immune dysfunction and inflammation,21 cancer,22 autism,23 Alzheimer’s,24 cardiovascular disease 25 26, endrocrine function 27, embryological development 28, and gastrointestinal disorders 29, While pharmaceutical companies are currently attempting to develop drugs in all of these areas to inhibit or enhance purinergic signaling 30, safety is an issue as the balance of these compounds at the cellular level is delicate, and both too much and too little adenosine and ATP are associated with disease. However, stimulating improved self-regulation of purinergic signaling through acupuncture treatment is likely both effective and safe.
In addition to biochemical actions, studies also demonstrate direct effects of acupuncture on the central nervous system. These include spinal reflex effects, where acupuncture stimulates muscle relaxation and changes in visceral organs. In the brain, acupuncture has been shown to change functional connectivity, decreasing activity in limbic structures associated with stress and illness while improving the regulation of the hypothalamus, pituitary, adrenal axis, the primary system that the body uses for regulating hormones and the physiological stress response 31. Additionally, acupuncture modulates parasympathetic activity, the branch of the nervous system associated with rest, relaxation, digestion and tissue healing 32.
REPORTING BIAS IN MEDICAL RESEARCH: A GLOBAL PROBLEM
Some critics who deny acupuncture’s effectiveness despite considerable evidence to the contrary try to make the case that research coming from China should be discarded from reviews. While this would be contrary to standards set by the Cochrane Collaboration, considered to be the foremost global authority on review methodology, these critics say that China only publishes positive studies, also known as ‘reporting bias,’ using a 1998 study as evidence 33.
Most research into acupuncture is conducted outside of China, but China does produce a large number of studies each year 34. While there is at times evidence of methodological issues in research coming out of China, in order for the argument against Chinese studies to be valid, there would need to be evidence that these methodological issues are limited to China or are considerably worse there. But does such evidence exist? Is research from China suspect, yet trustworthy if conducted elsewhere?
The question of the role of publication country on the quality of research was looked at recently. A 2017 review published in the Journal of Clinical Epidemiology that compared methodological and reporting quality of systematic reviews from China and the USA found that the quality was the same in both countries 35. However, when it comes to reporting bias, reviews show that the practice is common world-wide and not at all limited to China or any country in particular.
A recent review found that the quality and reporting in systematic reviews, the highest level of medical evidence, is the same in the United States and China.
A review of reporting bias in medical research found that this issue is highly prevalent worldwide. “Results of clinical research are largely underreported or reported with delay. Various analyses of research protocols submitted to institutional review boards and research ethics committees in Europe, the United States, and Australia found that on average, only about half of the protocols had been published” 36.
In the United States, the US Food and Drug Administration (FDA) approves new drugs based on trials submitted by the pharmaceutical companies who sell them. However, a review looking at 909 trials supporting 90 FDA approved drugs found that fewer than half of the research had been published. Not surprisingly, studies were far more likely to be published if they were considered to be ‘pivotal’ to the drug’s acceptance and if they showed a positive result 37.
Another important review measuring the impact of reporting bias found that the problem was “wide-spread in the medical literature.” They found evidence of reporting bias for 40 clinical indications for about 50 different pharmacological, surgical, diagnostic, and vaccine interventions. “Many cases involved the withholding of study data by manufacturers and regulatory agencies, or the active attempt by manufacturers to suppress publication. The ascertained effects of reporting bias included the overestimation of efficacy and the underestimation of safety risks of interventions” 38.
Improvements to this problem of unreliable evidence due to industry violations do not appear to be in progress. According to a 2017 appeal published in the British Medical Journal in response to “systematic bias, wastage, error and fraud in research underpinning patient care,” between 2009 and 2014, the drug industry received fines of US$13 billion for criminal behavior and civil infringements, and yet systematic changes preventing these fraudulent behaviours and doctoring of data have been lacking 39.
Acupuncture enjoys moderate to strong evidence of effectiveness in the treatment of 46 conditions and is considered safe in the hands of properly trained practitioners. This strong scientific support is impressive and helpful for patients in the context of a conventional healthcare system where nearly half of all treatments lack evidence for their use. Acupuncture is also considered cost-effective for a number of conditions where evidence is available. Comparatively, for many conditions it enjoys greater evidence than many conventional treatments and is relatively safer. Patients, medical professionals, and healthcare administrators can be confident that the recommendation of acupuncture for many patients is a safe, cost-effective, and evidence-based recommendation.