Plausible Mechanism of Sham Acupuncture Based on Biomarkers: A Systematic Review of Randomized Controlled Trials

Acupuncture is an ancient practice that has attracted great scientific interest over recent decades. One of the main challenges in understanding how this therapy works is the need to conduct studies that can separate its specific effects from placebo effects. To this end, researchers developed so-called "sham acupuncture" (or false acupuncture), which was intended to function as an inert control, similar to a sugar pill used in drug studies. Sham acupuncture was created to look identical to real acupuncture but without the treatment's specific physiological effects.

However, there has been growing questioning about whether this sham acupuncture is truly inactive or whether it also produces effects on the body.

This research aimed to evaluate whether there is a difference between real acupuncture and sham acupuncture when analyzing biological markers present in the blood (called biomarkers). The researchers conducted a systematic review, a type of study that gathers and analyzes all scientific work already published on a specific topic. They sought randomized clinical trials that compared the effects of real acupuncture versus sham acupuncture through measurement of substances in the blood. The methodology involved searching three large scientific databases (PubMed, EMBASE, and Cochrane) from inception through June 2021, with no language restrictions.

The authors included any type of sham acupuncture (such as superficial skin stimulation, non-penetrating needles, or false points) compared with real acupuncture, regardless of the participants' health condition.

The results revealed surprising findings that challenge the traditional notion of sham acupuncture. Of the 51 studies analyzed, involving 36 different blood biomarkers, the majority showed no significant differences between real and sham acupuncture. Only seven biomarkers showed differences between groups: VEGF, IgE, TNF-α, NGF, GABA, NPY, and VIP. These markers are related to inflammation processes, the immune system, and neurological modulation.

The most relevant finding is that in 29 of the 36 biomarkers studied, both real and sham acupuncture produced similar effects on the body. This suggests that sham acupuncture may not be as inactive as previously thought, as it appears to activate physiological mechanisms similar to traditional acupuncture.

For patients, these results bring important and encouraging implications. First, they suggest that even more superficial or different forms of needle stimulation may produce real benefits in the body, not merely placebo effects. This may explain why some patients report improvements even when receiving sham acupuncture in clinical studies. For healthcare providers, the findings indicate the need to rethink how acupuncture studies are conducted.

If sham acupuncture also produces physiological effects, then comparing real acupuncture with sham acupuncture may not be the best way to test treatment efficacy. This may explain why some studies fail to demonstrate the superiority of real acupuncture over sham, not necessarily because acupuncture does not work, but because both forms may be active. The results also suggest that different types of needle stimulation, even superficial ones, may activate nerve receptors and trigger similar physiological responses.

The study presents some important limitations that should be considered in interpreting the results. Clinical heterogeneity between studies was significant, as different health conditions, types of acupuncture, and treatment protocols were included. The limited number of studies for each specific biomarker also restricted the capacity for more detailed analyses. In addition, many of the included studies had a high risk of methodological bias, which may affect the reliability of the results.

The authors also acknowledge that other relevant biomarkers may exist that were not assessed, and that the search may not have captured all relevant studies, especially those published in regional databases such as Chinese and Korean ones.

In conclusion, this research offers important evidence that sham acupuncture may have physiological effects similar to real acupuncture, raising questions about its adequacy as an inert control in clinical studies. For patients interested in acupuncture, this suggests that different forms of needle stimulation may be beneficial, broadening therapeutic possibilities. For the scientific community, the results indicate the need to develop new control methods in acupuncture research and to reconsider how we interpret studies that compare real with sham acupuncture. Although more research is needed to confirm these findings, the study represents an important step toward better understanding the mechanisms of acupuncture and optimizing its clinical application, benefiting both patients and healthcare providers.