Methodological considerations regarding the combination of acupuncture and anti-inflammatory diet for depression in type 2 diabetes

Nutrition & Diabetes CORRESPONDENCE www.nature.com/nutd OPEN Methodological considerations regarding the combination of acupuncture and anti-inflammatory diet for depression in type 2 diabetes © The Author(s) 2026 1234567890();,: Nutrition and Diabetes (2026)16:14 ; doi.org/10.1038/s41387-026-00436-8 https:// We read with great interest the study by Irandoost et al. [1] entitled “The effects of an anti-inflammatory diet alone or in combination with acupuncture on mental health, anthropometric indices, and metabolic status in diabetic patients with depression: a randomized, controlled clinical trial.” This study investigates the potential of acupuncture to enhance both the physical and mental health of patients with type 2 diabetes mellitus who also experience mild to moderate depression. This topic holds significant clinical value and offers a robust research framework for evaluating the therapeutic efficacy of acupuncture. However, after a thorough review of the study’s design and data interpretation, we identify several issues that require further refinement in future related research. First, this study lacks a sham acupuncture control group, which may hinder the ability to exclude placebo effects and attention bias [2]. Although the paper states that “complete blinding was unfeasible due to the nature of the intervention,” the absence of a sham acupuncture group prevents us from determining whether the reduction in depression scores (MADRS) is attributable to the specific physiological effects of acupoints or merely to the nonspecific psychological effects of “being treated”—that is, the placebo effect. Secondly, the study reported that after an 8-week intervention, the combined treatment group exhibited a significant reduction in glycated hemoglobin (HbA1c) levels. HbA1c serves as an indicator of the average blood glucose levels throughout the lifespan of red blood cells, which is approximately 120 days. While the intensive 8-week intervention may begin to influence HbA1c, the significant changes observed within such a brief timeframe, along with the absence of statistically significant differences in fasting blood sugar (FBS) between groups during the same period, suggest that these results may be influenced by short-term fluctuations in water balance or other acute metabolic changes, rather than accurately reflecting the effects of glycemic control [3]. Third, the heterogeneity of antidiabetic drugs was not adequately controlled. Although patients using insulin and liraglutide were excluded, the category of ‘oral antidiabetic drugs’ encompasses multiple medications with distinct pharmacological mechanisms. If randomization failed to balance the distribution of drugs that possess weight-loss and anti-inflammatory effects across groups [4], the advantages observed in the combination therapy group regarding waist circumference and metabolic indicators might be partially confounded by indication bias. Fourth, the statistical design did not provide sufficient support for the claim of “synergistic interaction”. To demonstrate “synergistic interaction”, a 2 × 2 factorial design is typically required, including four groups: blank control, diet alone, acupuncture alone, and acupuncture+diet [5]. Since this study lacks a pure acupuncture group, the current data more appropriately suggest that acupuncture exhibits an “additive effect”. Furthermore, the data imply that the diet has minimal impact on alleviating depression, with improvements in mental health likely driven predominantly by acupuncture rather than by a “synergistic interaction”. In summary, the study offers valuable preliminary evidence that supports the efficacy of combined acupuncture as an integrated therapeutic approach. However, given the confounding factors discussed previously, well-designed future studies are necessary to validate these findings before acupuncture can be recommended as a standard clinical adjunct therapy. Meijie Shang1,2, Siyu Hu1,2, Haiyu Cao1,2, Xiaolei Li1,2 and ✉ Suzhao Zhang 1,2 1 Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China. 2 Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang, Hebei, China. ✉email: REFERENCES 1. Irandoost P, Firouzjaei A, Heshmati J, Sadeghi E, Ayati MH, Namazi N. The effects of an anti-inflammatory diet alone or in combination with acupuncture on mental health, anthropometric indices, and metabolic status in diabetic patients with depression: a randomized, controlled clinical trial. Nutr Diab. 2025;15:18. https:// doi.org/10.1038/s41387-025-00373-y. 2. Lund I, Näslund J, Lundeberg T. Minimal acupuncture is not a valid placebo control in randomised controlled trials of acupuncture: a physiologist’s perspective. Chin Med. 2009;4:1. https://doi.org/10.1186/1749-8546-4-1. 3. Fonseca V, Inzucchi SE, Ferrannini E. Redefining the diagnosis of diabetes using glycated hemoglobin. Diabetes Care. 2009;32:1344–5. https://doi.org/10.2337/ dc09-9034. 4. Lazzaroni E, Ben Nasr M, Loretelli C, Pastore I, Plebani L, Lunati ME, et al. Antidiabetic drugs and weight loss in patients with type 2 diabetes. Pharmacol Res. 2021;171:105782. https://doi.org/10.1016/j.phrs.2021.105782. 5. Byth K, Gebski V. Factorial designs: a graphical aid for choosing study designs accounting for interaction. Clin Trials. 2004;1:315–25. https://doi.org/10.1191/ 1740774504cn026oa. AUTHOR CONTRIBUTIONS Meijie Shang and Siyu Hu conceived the idea and prepared the initial draft of the manuscript. Haiyu Cao, Xiaolei Li and Suzhao Zhang refined the manuscript. All authors have read and approved the final version. Received: 10 February 2026 Revised: 25 April 2026 Accepted: 28 May 2026 Correspondence 2 FUNDING Correspondence and requests for materials should be addressed to Suzhao Zhang. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons.org/licenses/by-nc-nd/4.0/. Reprints and permission information is available at http://www.nature.com/ reprints © The Author(s) 2026 Traditional Chinese Medicine Innovation Special Project of Hebei Provincial Dep (...truncated)