Is sham acupuncture necessary in acupuncture clinical study?

Acupuncture is a therapy through physical stimulation by inserting a sharp, thin needle into the specific point on the body, with mechanical, electrical, or other physical manipulations, which stimulate nerve receptors both directly and indirectly through mechanical coupling via the connective tissue surrounding the needle. In general, the acupuncture stimulation, through the local reflex and central nervous system, induces endocrine, autonomic, and systemic behavioural responses. During past 20 years acupuncture studies have been extensively conducted worldwide, with a mean annual growth rate of 10.7%. It could be said that no other alternative medicines have been through such strict and detailed and scrutinized studies. Even though, the action mechanisms of acupuncture’s analgesic effect have been elucidated and the findings have been published on some top scientific journals.

There is a debate whether acupuncture clinical studies should be subjected to the standard drug therapy clinical trial, because acupuncture is not a medication. We know that efficacy of drug/medication can be assessed under ideal conditions of traditional randomized controlled, double-blinded, sham controlled trials. However, acupuncture is not a kind of medication therapy and is applied in routine circumstance. So the measurement of effectiveness such as comparative effectiveness research (CER), rather than efficacy used in standard drug therapy clinical trial, should be applied to acupuncture clinical studies. CER compares the benefits and harms of the best care options and produces evidence to support decision maker, which is a better option for public health. The real world evidence, more generalizable than the evidence produced by traditional randomized controlled trials, is better suited to inform real-world care decisions. With gradually understanding the nature of acupuncture, recently it was questioned whether it was necessary that sham control should be used in acupuncture clinical studies, because sham controlled study actually complicated result evidence base in some circumstance (Manheimer, 2011). Further, it has been suggested that assessment of the specific effect of acupuncture, by using sham acupuncture in an attempt to blind participants, could produce another limitation for clinical acupuncture trials by potentially attenuating the effects of ‘real’ acupuncture (Kim et al., 2017). Further discussion regarding study design and control interventions for acupuncture clinical trial is necessary.

Reference:

Manheimer E. Selecting a control for in vitro fertilization and acupuncture randomized controlled trials (RCTs): how sham controls may unnecessarily complicate the RCT evidence base. 2011, Fertil Steril. 95(8):2456-61.  https://www.ncbi.nlm.nih.gov/pubmed/21570069 

Kim TH. et al., What is lost in the acupuncture trial when using a sham intervention? Acupunct Med. 2017 Apr 29. pii: acupmed-2016-011333.   https://www.ncbi.nlm.nih.gov/pubmed/28456756

Acupuncture stimulation improved cognitive function in middle-aged people

Electro-acupuncture with low-frequency stimulation improved cognitive function in middle-aged women and men, reflected by the changes in P300 index. A report of pilot of randomized controlled clinical studies was published in journal of BMC Complementary and Alternative Medicine.

Aging is related to an increase in senile disorders such as Alzheimer’s disease. It has been recently reported that the number of patients with Alzheimer’s dementia is expected to reach 13.5 million by 2050 in the United States alone and will become a major problem worldwide over time. How to improve cognitive function is crucial to prevent senile-related conditions. The P300 is an important index that is used in clinical studies to evaluate reductions in memory and other cognitive functions and has been known to show decreased amplitude and delayed latency with aging. Acupuncture stimulation at some specific acupoints was reported to improve cognitive function and slow down the reduction of memory.

Recently Dr. KH Choi and colleagues conducted a pilot clinical study with randomised double-blinded controlled setting to evaluate the effect of low-frequency electro-acupuncture stimulation at BL62 and KI6 on cognitive function, using P300 index. Fifty-five healthy subjects in their 50s, including 26 males and 29 females were recruited and divided into real acupuncture (n=28) and sham acupuncture (n=27) groups. In real electro-acupuncture at an average of 24μA and 2 Hz stimulation at acupoints BL62 and KI6 lasted 30 mins each session, 12 sessions over one month. Brain activity of each subject was recorded by event related potentials (ERPs) of electroencephalogram before the first session and after the last session of acupuncture, then analysed using P300.

It was found that subjects in the real acupuncture group showed a tendency toward a decreasing P300 latency and increasing P300 amplitude after all 12 sessions of stimulation. In the women, the amplitude significantly increased at many perimeters, compared with sham group.

The authors suggested that the results of this study may serve as a foundation for the treatment of dementia and various brain disorders due to brain aging and impaired cognition. However, because the results of this study are limited to middle-aged women, further studies are necessary to determine the therapeutic effects in different age groups as well as in men and to discover the neurological mechanisms underlying the positive influence of low-frequency electrical stimulation on the brain.

Reference

KH Choi et al., Change in the P300 index–a pilot randomized controlled trial of low-frequency electrical stimulation of acupuncture points in middle-aged men and women. BMC Complementary and Alternative Medicine (2017) 17:246.    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415720/

Synergistic effect of Chinese herbal medicine with l-dopa in treating Parkinson’s

Although conventional treatments such as l-dopa and many more markedly improved motor symptoms of Parkinson’s, long-term use is associated with severe adverse effects that could significantly impact on the quality of life of patients with Parkinson’s. Alternative therapies such as Chinese herbal medicine is proved to be as effective as conventional medicine but with markedly less side-effect.

Very recently Dr. Ahn S and colleagues investigated whether the modified Cheong-gan-tang (淸肝湯 CGT, KD5040) would have synergistic effects with l-dopa on motor function and reduce l-dopa-induced dyskinesia. Modified Cheong-gan-tang (淸肝湯, KD5040), consisting of Paeonia lactiflora Pall, Ligusticum chuanxiong Hort, Angelica gigas Nakai, Bupleurum falcatum Linne, Gardenia jasminoides Ellis, and Paeonia suffruticosa Andrews plus Eugenia caryophyllata Thunb and Pogostemon cablin Bentham was co-administered with l-dopa to the Parkinson’s mouse model.

It was shown that co-administration of CGT with low-dose l-dopa synergistically improved the motor function. In addition, it significantly reversed MPTP-induced lowering of substance P, improved enkephalin levels, both are neuropeptides involved in the motor regulation in the basal ganglia. Further, co-administration of both CGT and l-dopa ameliorated abnormal reduction in glutamate content in the motor cortex. Moreover, modified CGT significantly lowered abnormal involuntary movements and controlled l-dopa-induced abnormal levels of striatal FosB, pDARPP-32, pERK, and pCREB, which is the early gene expression pathway regulating occurrence of involuntary movement.

The findings of study suggested that modified CGT can be a possible candidate for adjunct therapy in treating motor dysfunction and dyskinesia in PD patients.

Reference

Ahn S et al., Effects of a combination treatment of KD5040 and L-dopa in a mouse model of Parkinson’s disease. BMC Complementary and Alternative Medicine (2017) 17:220.  https://www.ncbi.nlm.nih.gov/pubmed/28424060

Acupuncture significantly improved symptoms of narcolepsy – a case report

A patient (male, 45-year old) diagnosed with narcolepsy by the specialist about a year ago. Recently, he came to me for acupuncture treatment due to the worsen conditions. His narcolepsy was presented with poor interrupted night sleep and excessive daytime tiredness with at least 2 uncontrollable sleep attacks a day which lasted from a few seconds to a few minutes. His day time sleepiness has been for a couple of years. His cataplexy occurred when he was laughing or angry with someone and was presented as sudden head slump down or the jaw dropping for a few seconds and even fell down on the ground. The patient has had bad sleep for decades. He hasn’t taken any medication.

The patient was treated with manual acupuncture on many acupoints including BL62, KI6; GV20, EX-HN1, HT7, PC6, ST36, SP6, SP9 for 30 min twice a week for two weeks. After two sessions of acupuncture the patient had good sleep for a consecutive three-night and felt energetic. His daytime sleep attack reduced. After six-session treatment, the severity of cataplexy episode attack was markedly reduced. He could avoid fell down and held himself up when episode was occurring. When he was laughing, the anticipated episode didn’t happen. Then acupuncture was applied on above acupoints once a week. It was shown that the consecutive good sleep could last up to 4 or 5 nights after one session of acupuncture treatment. Daytime sleep attack was no longer an issue and cataplexy episode occurred in a minor level even with laughing or big mood swing during this time period. Now therapeutic effect of one session of acupuncture could last up to 6-7 days. The patient is very pleased.

Traditional Chinese medicine believes that ying-qi and wei-qi disharmony and imbalance of yin and yang may be the cause of narcolepsy. Ying-qi is running though Yin Qiao vessel and wei-qi is running though Yang Qiao vessel. Both Yin Qiao vessel and Yang Qiao vessel are believed to be part of body defence system, equalling to immune system in convention medicine. Modulation the activity of both vessels by stimulating corresponding acupoints on the vessels leads to rebalance body’s ying-qi and wei-qi and yin and yang. This may result in the improved immune system and rebalanced the levels of neurotransmitters or neuromodulators, in particular orexin (or hypocretin) in the brain leading to improvement of narcoleptic symptoms.

Acupuncture has been recommended as one of the favourable nonpharmacologic treatments for low back pain by American College of Physicians

Recently, acupuncture, an important part of traditional Chinese medicine, has been recommended as one of the favourable nonpharmacologic therapies for low back pain by American College of Physicians. Two reports published on journal of Ann Intern Med in February 2017 by Chou et al., 2017, and Qaseem et al., 2017 made the recommendation.

Lower back pain is one of the most common reasons for clinic visits in the United States. It is associated with increased healthcare costs as well as lost wages and decreased work productivity. Acute back pain generally lasts less than 4 weeks and usually resolves on its own. Subacute low back pain is defined as lasting 4 to 12 weeks, while chronic back pain lasts over 12 weeks. Up to 30% of patients report persistent low back pain up to 1 year after experiencing an acute episode. One in five report substantial limitations in activity, according to background information in the articles.

To develop the guideline, the ACP reviewed randomized controlled trials and systematic reviews of studies evaluating noninvasive, nondrug, and drug therapy for low back pain in adults. To be included, studies had to be published in English between January 2008 and November 2016. The authors identified earlier studies using the 2007 ACP/American Pain Society systematic reviews. The agency evaluated outcomes including reduction or elimination of back pain and number of back pain episodes, improvement in back-specific function, improvement in health-related quality of life, reduction in work disability, patient satisfaction, and adverse events. The guidelines and evidence reviews also underwent peer review and a public comment period.

Overall, the new guidelines emphasize conservative treatment. First-line therapy should incorporate nondrug therapies. New evidence supports acupuncture in acute low back pain alongside with massage, or spinal manipulation; and tai chi and acupuncture in chronic low back pain alongside exercise, multidisciplinary rehabilitation, yoga, motor control exercise, progressive relaxation. Nonsteroidal anti-inflammatories (NSAIDs) or muscle relaxants should be considered when nondrug therapy fails. The guidelines strongly discourage the use of opioids (which can be associated with addiction and accidental overdose).

Reference

Chou R, Deyo R, Friedly J, Skelly A, Hashimoto R, Weimer M, Fu R, Dana T, Kraegel P, Griffin J, Grusing S, Brodt ED. Nonpharmacologic Therapies for Low Back Pain: A Systematic Review for an American College of Physicians Clinical Practice Guideline. Ann Intern Med. 2017 Apr 4;166 (7):493-505.  https://www.ncbi.nlm.nih.gov/pubmed/28192793

Qaseem A, Wilt TJ, McLean RM, Forciea MA; Clinical Guidelines Committee of the American College of Physicians. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline from the American College of Physicians. Ann Intern Med. 2017 Apr 4;166 (7):514-530.   http://annals.org/aim/article/2603228/noninvasive-treatments-acute-subacute-chronic-low-back-pain-clinical-practice

Mechanism of electroacupuncture-induced tissue repair

Electroacupuncture (EA) stimulation at some immune acupoints such as L14, LI11, DU20, DU14, ST36 and LV3 in both humans and rats activated hypothalamus and enhanced sympathetic nervous system (SNY) function, leading to mobilization of mesenchyals stem cells (MSC). EA-induced mobilization of circulating MSC increased anti-inflammation products; markedly reduced pain sensitivity and enhanced tissue repair. The study was published in journal of Stem Cells recently.

Recently a collaboration of acupuncture study by many research groups in the United States investigated the mechanism responsible for the beneficial systemic effects and healing associated with acupuncture in both humans and models.

First, the fMRI studies in both humans and models found that EA stimulation at L14, LI11, DU20, DU14 acupoints increased functional connectivity between the anterior hypothalamus and the amygdala and mobilized MSC into the systemic circulation. MSC were characterized as adipocyte-derived MSC in human, whereas, MSC were considered more heterogeneous in models.

Then, Pharmacological disinhibition of model hypothalamus by administration of the GABAA receptor antagonist bicuculline enhanced SNS activation and similarly resulted in a release of MSC into the circulation.

Finally, in models with partial rupture of the Achilles tendon, EA stimulation reduced mechanical hyperalgesia, increased anti-inflammation products such as serum IL‐10 and enhanced tendon remodelling and tissue repair.

The study suggested that EA may serve as way of facilitating tissue repair following by supplying high level of circulating MSC into the circulation and could be used to treat acute or chronic conditions associated with inflammation.

 Reference

Salazar TE et al., Electroacupuncture Promotes CNS-Dependent Release of Mesenchymal Stem Cells. Stem Cells. 2017 Mar 16. doi: 10.1002/stem.2613.     https://www.ncbi.nlm.nih.gov/pubmed/28299842

Acupuncture improved the symptoms and quality of life in patients with lumbar spinal stenosis

Acupuncture treatment showed that it could relieve pain and improve quality of life in patients with lumbar spinal stenosis (LLS). The report was published in Journal of Acupuncture and Meridian Studies.

Lumbar spinal stenosis is a narrowing of the spinal canal in the lower back, known as lumbar area. This usually happens when bone or tissue-or both-grow in the opening of the spinal canal, caused commonly by spondylosis or degenerative arthritis. Neurogenic pain of LLS is normally exacerbated by walking, standing and/or maintaining certain postures and relieved with sitting or lying. Other symptoms of LLS include sensory loss and weakness of legs, reflecting involvement of spinal nerve roots within lumbar spinal canal. Although medication is effective in relieving symptoms temporarily and surgical procedures will improve the conditions in some cases, none of the treatments is curative.

Dr. MJ Hadianfard and colleagues in Iran conducted a clinical study to assess the effectiveness of acupuncture on patients with LLS. Twenty-four patients with LLS were recruited for the study and were given acupuncture on following acupoints: bilateral BL-23, BL-25, BL-26, BL-37, BL-40, BL-54, BL-57, LI-4, BL-60, DU-3, DU-4, and DU-20 for 30 minutes per session, three sessions a week and 10 sessions in total. The visual analogue scale (VAS) and Short Form-36 Health Survey (SF-36) were monitored for pain and quality of life before treatment, immediate after final treatment and 6-week follow-up. Patients did not receive other treatments during the course of acupuncture treatment.

It was shown that acupuncture treatment significantly improved pain and quality of life such as emotions, vitality, general health, bodily pain, and physical well-being not only immediate after final treatment and but maintained 6-week after treatment. There was no adverse effect reported.

The study demonstrated that acupuncture was able to relieve pain and improve the quality of life of patients with LLS.

Reference:

Hadianfard MJ et al., Effect of Acupuncture on Pain and Quality of Life in Patients with Lumbar Spinal Stenosis: A Case Series Study. J Acupunct Meridian Stud. 2016 Aug;9(4):178-82.    https://www.ncbi.nlm.nih.gov/pubmed/27555222