 Regarding cancer patients, The US NIH National Cancer Institute states that acupuncture may cause physical responses in nerve cells, the pituitary gland, and the brain – releasing proteins, hormones, and chemicals that are proposed to affect blood pressure, body temperature, immune activity, and endorphin release.A 2012 meta-analysis concluded that the mechanisms of acupuncture "are clinically relevant, but that an important part of these total effects is not due to issues considered to be crucial by most acupuncturists, such as the correct location of points and depth of needling ... [but is] ... associated with more potent placebo or context effects".Commenting on this meta-analysis, both Edzard Ernst and David Colquhoun said the results were of negligible clinical significance.