Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Acupoint injection increases the efficacy of vitamin B12 for diabetic neuropathy: a meta-analysis and trial sequential analysis

Abstract

This study aims to systematically evaluate the efficacy and safety of vitamin B12 acupoint injections compared to other administration routes in treating diabetic neuropathy (DN). We included 20 randomized controlled trials published before March 1, 2024, sourced from eight public databases, involving 1688 participants. Subsequently, we recorded their basic data, investigated their risk of bias, and then carried out a meta-analysis and trial sequential analysis (TSA). The meta-analysis revealed that compared to other administration routes of vitamin B12, acupoint injection significantly improved the clinical effectiveness proportion by 28% (risk ratio [RR] 1.28, 95% confidence interval [CI] 1.22–1.35), peroneal nerve motor nerve conduction velocity (MNCV) by 4.43 m/s (MD 4.43, 95% CI 2.83–6.03), peroneal nerve sensory nerve conduction velocity (SNCV) by 3.82 m/s (MD 3.82, 95% CI 3.23–4.41), median nerve MNCV by 5.48 m/s (MD 5.48, 95% CI 4.71–6.24), and median nerve SNCV by 4.62 m/s (MD 4.62, 95% CI 3.84–5.39) in patients with DN, while having no significant impact on fasting blood glucose (FBG) (MD −0.18, 95% CI −0.44 to 0.08), 2-h postprandial blood glucose (2h-PBG) (MD −0.02, 95% CI −0.36 to 0.33), and the adverse event incidence (RR 1.44, 95% CI 0.44–4.70). TSA indicated that except for FBG, 2h-PBG, and adverse event incidence, the remaining meta-analysis results were conclusive. These findings indicate that compared to other administration routes of vitamin B12, acupoint injection improves neurological function in patients with DN without increasing adverse events and economic burden, suggesting that it may be the optimal administration route for vitamin B12.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4: Forest plots of the meta-analysis on the nerve conduction velocity.
Fig. 5: Forest plots of the meta-analysis on the blood glucose.

Similar content being viewed by others

Data availability

The data from this study are available upon request to the corresponding author.

References

  1. Tabish SA. Is Diabetes becoming the biggest epidemic of the twenty-first century?. Int J Health Sci. 2007;1:5–8.

    Google Scholar 

  2. Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diab Res Clin Pr. 2022;183:109119.

    Article  Google Scholar 

  3. Feldman EL, Callaghan BC, Pop-Busui R, Zochodne DW, Wright DE, Bennett DL, et al. Diabetic neuropathy. Nat Rev Dis Prim. 2019;5:42.

    Article  PubMed  Google Scholar 

  4. Selvarajah D, Kar D, Khunti K, Davies MJ, Scott AR, Walker J, et al. Diabetic peripheral neuropathy: advances in diagnosis and strategies for screening and early intervention. Lancet Diab Endocrinol. 2019;7:938–48.

    Article  Google Scholar 

  5. Callaghan BC, Little AA, Feldman EL, Hughes RAC. Enhanced glucose control for preventing and treating diabetic neuropathy. Cochrane Database Syst Rev. 2012;2012:CD007543.

  6. Schlesinger S, Herder C, Kannenberg JM, Huth C, Carstensen-Kirberg M, Rathmann W, et al. General and abdominal obesity and incident distal sensorimotor polyneuropathy: insights into inflammatory biomarkers as potential mediators in the KORA F4/FF4 cohort. Diab care. 2019;42:240–7.

    Article  CAS  Google Scholar 

  7. Partanen J, Niskanen L, Lehtinen J, Mervaala E, Siitonen O, Uusitupa M. Natural history of peripheral neuropathy in patients with non-insulin-dependent diabetes mellitus. N Engl J Med. 1995;333:89–94.

    Article  CAS  PubMed  Google Scholar 

  8. Gordois A, Scuffham P, Shearer A, Oglesby A, Tobian JA. The health care costs of diabetic peripheral neuropathy in the US. Diab Care. 2003;26:1790–5.

    Article  Google Scholar 

  9. Callaghan BC, Price RS, Feldman EL. Distal symmetric polyneuropathy: a review. JAMA. 2015;314:2172–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ismail-Beigi F, Craven T, Banerji MA, Basile J, Calles J, Cohen RM, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet. 2010;376:419–30.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Didangelos T, Karlafti E, Kotzakioulafi E, Margariti E, Giannoulaki P, Batanis G, et al. Vitamin B12 supplementation in diabetic neuropathy: a 1-year, randomized, double-blind, placebo-controlled trial. Nutrients. 2021;13:395.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ryan-Harshman M, Aldoori W. Vitamin B12 and health. Can Fam Phys. 2008;54:536–41.

    Google Scholar 

  13. Pflipsen MC, Oh RC, Saguil A, Seehusen DA, Seaquist D, Topolski R. The prevalence of vitamin B(12) deficiency in patients with type 2 diabetes: a cross-sectional study. J Am Board Fam Med. 2009;22:528–34.

    Article  PubMed  Google Scholar 

  14. Bell DSH. Metformin-induced vitamin B12 deficiency can cause or worsen distal symmetrical, autonomic and cardiac neuropathy in the patient with diabetes. Diab Obes Metab. 2022;24:1423–8.

    Article  CAS  Google Scholar 

  15. Schleicher E, Didangelos T, Kotzakioulafi E, Cegan A, Peter A, Kantartzis K. Clinical pathobiochemistry of vitamin B12 deficiency: improving our understanding by exploring novel mechanisms with a focus on diabetic neuropathy. Nutrients. 2023;15:2597.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Randaccio L, Geremia S, Demitri N, Wuerges J. Vitamin B12: unique metalorganic compounds and the most complex vitamins. Molecules. 2010;15:3228–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Thakkar K, Billa G. Treatment of vitamin B12 deficiency-methylcobalamine? Cyancobalamine? Hydroxocobalamin?-clearing the confusion. Eur J Clin Nutr. 2015;69:1–2.

    Article  CAS  PubMed  Google Scholar 

  18. Buesing S, Costa M, Schilling JM, Moeller-Bertram T. Vitamin B12 as a treatment for pain. Pain Physician. 2019;22:E45–E52.

    Article  PubMed  Google Scholar 

  19. Yazidi M, Kamoun E, Hadj Taieb S, Rejeb O, Mahjoub S, Maryam S, et al. Vitamin B12 deficiency in long-term metformin treated type 2 diabetic patients: prevalence and risk factors in a Tunisian population. Chronic Illn. 2024;20:631–9.

    Article  PubMed  Google Scholar 

  20. Tandon R, Thacker J, Pandya U, Patel M, Tandon K. Parenteral vs oral vitamin B12 in children with nutritional macrocytic anemia: a randomized controlled trial. Indian Pediatr. 2022;59:683–7.

    Article  PubMed  Google Scholar 

  21. Elangovan R, Baruteau J. Inherited and acquired vitamin B12 deficiencies: which administration route to choose for supplementation?. Front Pharm. 2022;13:972468.

    Article  CAS  Google Scholar 

  22. Wang Z, Shi X. Research progress of acupoint injection in treating diabetic peripheral neuropathy China’s. Naturopathy. 2022;30:121–5.

    Google Scholar 

  23. Oh JE, Kim SN. Anti-inflammatory effects of acupuncture at ST36 point: a literature review in animal studies. Front Immunol. 2021;12:813748.

    Article  CAS  PubMed  Google Scholar 

  24. Zhu J, Li J, Yang L, Liu S. Acupuncture, from the ancient to the current. Anat Rec. 2021;304:2365–71.

    Article  Google Scholar 

  25. Sha T, Gao LL, Zhang CH, Zheng JG, Meng ZH. An update on acupuncture point injection. QJM Monthly J Assoc Phys. 2016;109:639–41.

    CAS  Google Scholar 

  26. Feng Y, Fang Y, Wang Y, Hao Y. Acupoint therapy on diabetes mellitus and its common chronic complications: a review of its mechanisms. BioMed Res Int. 2018;2018:3128378.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Liu L, Jiang C, Zhao Z. Effects of salvia miltiorrhiza Ligustrazine injection combined with mecobalamin on diabetic peripheral neuropathy and oxidative stress response. Chin Herb Med. 2019;50:2670–4.

    Google Scholar 

  28. Zhou J, Li X, Liang Y, Wang Z. Efficacy of acupoint injection of methycobal in the treatment of diabetic peripheral neuropathy in 45 cases. J Clin Acupunct Moxibustion. 2005;2005:39–40+67.

    Google Scholar 

  29. Li S, Wang K, Hou J, Yan H, Li J. Clinical research progress on external treatment of traditional Chinese medicine in the treatment of diabetic peripheral neuropathy. Yunnan J Traditional Chin Med Mater Med. 2018;39:82–84.

    Google Scholar 

  30. Chen H, Ma G, Ye T, Tian Y. Clinical observation on the treatment of diabetic lower limb neuropathy by acupoint injection of methycobal. J Clin Acupunct Moxibustion. 2012;28:41–42.

    CAS  Google Scholar 

  31. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Cao R. Mecobalamin Zusanli acupoint injection in adjuvant treatment on diabetic peripheral neuropathy of lower limb. Hebei Med. 2015;21:323–5.

    CAS  Google Scholar 

  33. Chen D, Yu J. Clinical observation on acupuncture point injection methycobal for diabetic peripheral neuropathy of four extremity. J Clin Acupunct Moxibustion. 2015;31:39–42.

    CAS  Google Scholar 

  34. Deng X, Zhao W, Tang A, Li S, Liu C, Luo G, et al. Acupoint injection of methycobal to treat diabetes observation on the efficacy of neuropathy. J Guangxi Univ Chin Med. 2007;2007:17–19.

    Google Scholar 

  35. Guo H, Zhao S, Li C, Guo Y, Zhang X. Clinical experience of methylcobalamin Zusanli acupoint injection in the treatment of diabetic peripheral neuropathy. In: Proceedings of the 3rd Shandong Province Academic Symposium on Integrated Traditional Chinese and Western Medicine Neurology, pp320–323. Neurology Professional Committee of Shandong Association of Integrative Medicine: Jinan, Shandong, China; 2011.

  36. Huang C. Efficacy of cobamamide injection at acupoints on DPN. Clin J Chin Med. 2018;10:55–57.

    Google Scholar 

  37. Li Z, He F, Xiao H, Zhang K. Methylcobalamin acupoint injection in the treatment of diabetic peripheral neuropathy. Qingdao Med J. 2009;41:36–37.

    CAS  Google Scholar 

  38. Liu Y. Exploration of the efficacy and safety of different injection modalities of methylcobalamin in diabetic peripheral neuropathy. Chin Sci Technol J Database. 2021;2021:0097–8.

    Google Scholar 

  39. Mo G, Tan L, Huang X. Clinical observation on 40 cases of diabetic peripheral neuropathy treated with methylcobalamin acupoint injection. Jiangsu J Traditional Chin Med. 2011;43:63–64.

    Google Scholar 

  40. Sun J, Han Y. Observation on the efficacy of methylcobalamin acupoint injection in the treatment of diabetic lower limb peripheral neuropathy. Mod J Integr Traditional Chin West Med. 2011;20:2512–3.

    Google Scholar 

  41. Wen X. Clinical observation on the treatment of peripheral neuropathy in type 2 diabetes mellitus with methylcobalamin acupoint injection. J North Pharm. 2014;11:30–31.

    Google Scholar 

  42. Wu L, Liu Y, Tang Q, Wang R, Xi F, Zhang T, et al. Influence of point injection with meridian fiowing Na Zhi method on diabetic patients with peripheral neuropathy. Chin Nurs Res. 2015;29:3418–9.

    Google Scholar 

  43. Xie Q, Hua D, Zhang L, Chen X. Observation on the efficacy of drug acupoint injection in the treatment of diabetic peripheral neuropathy. J Practical Traditional Chin Med. 2016;32:1189–90.

    Google Scholar 

  44. Xie Q, Chen D, Chen X. Effects of acupoint injection on serum SP in patients with diabetic peripheral neuropathy and clinical observation. Jiangxi J Traditional Chin Med. 2022;53:57–59.

    Google Scholar 

  45. Xu Z, Dong C, Ren M, Zhao X, Ma L, Zhang Y, et al. Observation on the efficacy of bilateral foot-sanli acupoint injection with adenosylcobalamin in patients with diabetic paralysis of the qi deficiency and blood stasis type. World Latest Med Inf. 2020;20:172–4.

    Google Scholar 

  46. Yang L, Li S, Zhu Y. Clinical study on 38 cases of diabetic peripheral neuropathy treated with methylcobalamin acupoint injection. Hebei J Traditional Chin Med. 2009;31:421–2.

    CAS  Google Scholar 

  47. Zhang L. Clinical study of acupuncture point injection in the treatment of diabetic peripheral neuropathy. Practical Clin J Integr Traditional Chin West Med. 2022;22:103–5+116.

    Google Scholar 

  48. Zhao C, Zhang X, Zhu J, Wang M, Dou Y, Wang J. Efficacy of acupoint injection of methylcobalamin combined with intravenous infusion of alpha-lipoic acid in the treatment of diabetic peripheral neuropathy. Shanxi Med J. 2016;45:579–80.

    Google Scholar 

  49. Zhao D, Zhang F, Meng Y. Observations on the treatment of diabetic peripheral neuropathy by acupoint injection. Inf Traditional Chin Med. 2009;26:69–70.

    Google Scholar 

  50. Fei W, Shi X, Zhang D, Lian G. Observation of curative effect of vitamin B12 and its two active forms injections at Zusanli acupoint inthe treatment of diabetic distal symmetric polyneuropathy. Gansu Med J. 2022;41:705–7.

    Google Scholar 

Download references

Funding

This study was funded by the National Natural Science Foundation of China [U21A20411].

Author information

Authors and Affiliations

Contributions

YYu and RY designed the study. YYu, TZ, and XL collected and organized data. LL and YYin performed the statistical analysis. YYu, TZ, XL, LL, and YYin wrote the manuscript. RY reviewed and revised the manuscript. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Rong Yu.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethical approval

This study involved the review and analysis of published literature and did not involve any human or animal subjects. Therefore, ethical approval was not required.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, Y., Zhou, T., Li, L. et al. Acupoint injection increases the efficacy of vitamin B12 for diabetic neuropathy: a meta-analysis and trial sequential analysis. Eur J Clin Nutr (2025). https://doi.org/10.1038/s41430-025-01631-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41430-025-01631-z

Search

Quick links